Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Prolactin is secreted by the anterior pituitary gland under negative control by dopamine, which is secreted by the hypothalamus. The only physiological function of prolactin is the stimulation of milk production. In normal individuals, the prolactin level rises in response to physiologic stimuli such as nipple stimulation, sleep, exercise, sexual intercourse, and hypoglycemia. Pathologic causes of hyperprolactinemia include prolactin-secreting pituitary adenoma (prolactinoma), diseases of the hypothalamus, primary hypothyroidism, section compression of the pituitary stalk, chest wall lesions, renal failure, and ectopic tumors.
Hyperprolactinemia may also be caused by the presence of a high-molecular–mass complex of prolactin called macroprolactin (typically due to prolactin bound to immunoglobulin). In this situation, the patient is asymptomatic. Hyperprolactinemia attributable to macroprolactin is a frequent cause of misdiagnosis and mismanagement of patients. Macroprolactin should be considered if, in the presence of elevated prolactin levels, signs and symptoms of hyperprolactinemia are absent, or pituitary imaging studies are not informative.
Determining biologically active levels of prolactin, in asymptomatic patients with elevated prolactin levels
Ruling out the presence of macroprolactin
When the percentage of the precipitated prolactin (complexed) fraction of total prolactin is <50%, the specimen is considered negative for macroprolactin. When total prolactin exceeds the upper reference limit and macroprolactin is negative, other causes for hyperprolactinemia should be explored.
When the percentage of the precipitated (complexed) prolactin fraction of total prolactin is > or =50%, the specimen is considered positive for the presence of macroprolactin.
Following macroprolactin precipitation, a patient whose unprecipitated prolactin level is greater than the upper limit of the total prolactin reference range may have hyperprolactinemia.
See PRL/8690 Prolactin, Serum for interpretation of prolactin levels.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Demonstration of the presence of macroprolactin does not exclude the possibility of concomitant presence of pituitary adenoma. Results should be interpreted in conjunction with clinical findings.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
< or =18 years: not established
>18 years: 4.0-15.2 ng/mL
< or =18 years: not established
>18 years: 4.8-23.3 ng/mL
Percent of the precipitated (complexed) prolactin fraction of the total prolactin <50% (considered negative for macroprolactin)
Unprecipitated prolactin levels are expected to be within the total prolactin reference range.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Fahie-Wilson M: In hyperprolactinemia, testing for macroprolactin is essential. Clin Chem 2003;49(9):1434-1436
2. Gibney J, Smith TP, McKenna TJ: Clinical relevance of macro-prolactin. Clin Endocrinol 2005;62:633-643