Prolactin

Order Code

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2800

Preferred Specimen

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Collect 2 mL of serum using an SST tube. Allow the sample to clot upright for a minimum of 30 minutes before centrifuging it within 2 hours of collection. Store the sample refrigerated.
Note: Avoid collecting specimens from patients undergoing high-dose biotin therapy (>5 mg/day) until at least 8 hours after the last biotin dose.

ContainerType

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Serum separator tube

Alternate Specimen Requirements

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Obtain 2 mL of serum in a plain red-top tube. Allow the sample to clot upright for at least 60 minutes, then centrifuge and transfer the serum into a plastic transport tube within 2 hours of collection. Ensure the tube is clearly labeled as serum from a plain red-top tube. Refrigerate the sample.
Note: Do not collect samples from patients receiving high-dose biotin therapy (>5 mg/day) until a minimum of 8 hours after the last biotin administration.

Minimum Volume

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Adult: 0.5 mL serum
Pediatric: 0.2 mL serum (does not allow for repeat or
additional testing).

Transport Temperature

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Refrigerated

Expected Turnaround Time

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1-2 days

Specimen Stability

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5 days room temperature; 2 weeks refrigerated; 6 months frozen. Allow only one freeze/thaw cycle

Methodology

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Roche COBAS Electrochemiluminescent Immunoassay (ECLIA) this method has been standardized against the 3rd irp WHO reference standard 84/500.

Overview

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Prolactin (PRL) is a hormone secreted by the anterior pituitary gland and is regulated by the hypothalamus primarily through dopamine’s inhibitory effects. The primary role of PRL is to promote breast development and lactation during and after pregnancy. Elevated prolactin levels (hyperprolactinemia) are commonly linked to clinical disorders in both males and females, with symptoms such as menstrual irregularities, sexual dysfunction, and infertility. The most frequent cause of hyperprolactinemia is prolactin-secreting pituitary tumors known as prolactinomas, though any condition that disrupts dopamine release (the natural inhibitor of prolactin) may also lead to increased prolactin levels.

Excess prolactin suppresses gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus, leading to reduced pituitary release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This decrease results in lowered estrogen and progesterone production in females and decreased testosterone levels in males, which contributes to the range of symptoms observed (McPherson, 2011; Snyder, 2013).

Clinical Significance

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• The principal clinical use for PRL levels is in the diagnosis of PRL-secreting pituitary adenomas. In this clinical setting, PRL values must be interpreted together with imaging studies.
  • Males may present with sexual dysfunction (low testosterone, hypogonadism), infertility, visual problems, headache
  • Females may present with oligomenorrhea, amenorrhea, infertility, galactorrhea
• Evaluate galactorrhea
• Evaluate menstrual irregularity: amenorrhea, oligomenorrhea, change in flow
• Evaluate male and female infertility
• Evaluate male sexual dysfunction/hypogonadism
• Evaluation of mass effect symptoms ( headaches and visual field changes)
• Monitor response to treatment in hyperprolactinemia

Additional Information

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Prolactin circulates in serum in several forms, each with differing biological activity. The monomeric form is the most abundant and bioactive, comprising approximately 90% of total circulating prolactin. Big prolactin has minimal biological activity and represents a small fraction of total prolactin. Macroprolactin, or big-big prolactin, is a complex of prolactin bound to IgG (an antiprolactin autoantibody), making up a smaller portion of total serum prolactin.

Dopamine secretion from the hypothalamus inhibits prolactin release from the pituitary gland. Conversely, several hormones stimulate prolactin secretion, including thyrotropin-releasing hormone (TRH), vasoactive intestinal polypeptide, epidermal growth factor, and estrogen. Prolactin secretion occurs in pulses following a circadian rhythm, with peak levels typically observed in the early morning and lowest levels around midday. Physiologic factors such as sleep, exercise, stress, and hyperglycemia can cause transient increases in serum prolactin.

Prolactinomas are the most common type of pituitary adenoma, accounting for 25% to 40% of cases. They may be asymptomatic or present with clinical signs. Over 80% of prolactinomas in reproductive-age women are microadenomas (<10 mm). In this group, symptoms such as amenorrhea, irregular menstrual cycles, infertility, and galactorrhea are common indicators. In males and older women, prolactinomas often lack these symptoms and are typically diagnosed later due to mass effects such as visual disturbances or headaches. Macroadenomas (>10 mm) usually exhibit prolactin levels exceeding 250 ng/mL. Malignant prolactinomas are rare, with only about 50 cases reported.

Interpretative Information

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Increased prolactin

• Pregnancy and lactation
• Prolactin secreting pituitary adenoma (prolactinoma)
• Medications including amphetamines, antipsychotics, androgens, chlorpromazine, cimetidine, danazol, estrogens, fluoxetine, isoniazid, methyldopa, metoclopramide, monoamine oxidase inhibitors, opiates, phenothiazines, reserpine, tricyclic antidepressants, and verapamil. Patient medications should be known and authoritative source of drug information consulted.
• Medical conditions including hypothyroidism, renal failure, cirrhosis, and chest wall trauma/surgery
• Other pituitary tumors or parasellar tumors inhibiting dopamine release by compressing the pituitary stalk
• Idiopathic prolactinemia (a diagnosis of exclusion)
• Hypothalamus disease or disorder
• Macroprolactinemia

Decreased prolactin

• Sheehan syndrome ( postpartum pituitary necrosis)
• Pituitary and extrapituitary tumors
• Treatment of a pituitary or extrapituitary tumor
• Infections ( ex: tuberculosis and histoplasmosis)
• Infiltrative diseases, such as hemochromatosis and sarcoidosis

Limitations

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• Patients with asymptomatic hyperprolactinemia should be tested for macroprolactinemia to avoid a false-positive diagnosis of prolactinoma. Because these macromolecules of prolactin cannot bind to the prolactin receptor, they do not produce typical symptoms of elevated prolactin, however they react with immunoassays and produce falsely high PRL results. Testing involves polyethylene glycol extraction and centrifugation followed by immunoassay to rule-out macroprolactin.
• The “high dose hook effect” should be considered in patients with a large pituitary tumor and prolactin levels that do not correlate (mildly elevated prolactin). The hook effect is the result of extremely high concentrations of prolactin which saturate assay antibody-binding sites yielding a falsely low result. Serial dilutions of the specimens should be performed.
• Prolactin levels can be elevated after sexual activity, exercise, lactation, and stressful venipuncture (Bolyakov, 2011)

References

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Diagnostic Role

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The differential diagnosis of hyperprolactinemia includes drug side effect, PRL-secreting pituitary adenoma, and other diseases of the hypothalamic-pituitary stalk region. Rare causes include renal disease, primary hypothyroidism, and endogenous estrogen overproduction.

Test Setup Days

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Monday through Friday PM shift

CPT

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84146 LOINC: 2842-3

Reference Range

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MALE: 4.0-26.0 NG/ML
FEMALE (NON-PREGNANT):
1-9 YEARS: 4.0-26.0 NG/ML
>=10 YEARS: 5.0-37.0 NG/ML

UNIT CODE	UNIT CODE NAME	ANALYTE	GENDER	AGE	REFERENCE RANGE	Units of Measure
2800	PROLACTIN	PRLCTN	NOT SPECIFIED	0Y	4.0-37.0	NG/ML
2800	PROLACTIN	PRLCTN	NOT SPECIFIED	9Y	4.0-26.0	NG/ML
2800	PROLACTIN	PRLCTN	NOT SPECIFIED	150Y	4.0-37.0	NG/ML
2800	PROLACTIN	PRLCTN	MALE	ALL	4.0-26.0	NG/ML
2800	PROLACTIN	PRLCTN	FEMALE	0Y	5.0-37.0	NG/ML
2800	PROLACTIN	PRLCTN	FEMALE	9Y	4.0-26.0	NG/ML
2800	PROLACTIN	PRLCTN	FEMALE	150Y	5.0-37.0	NG/ML