What investigations should be done for a patient with suspected hyperprolactinemia?

From the Guidelines

For a patient with suspected hyperprolactinemia, initial investigations should include a serum prolactin measurement in a single blood sample collected at any time of day, as a single measurement is sufficient to assess hyperprolactinemia 1. This approach is supported by the consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence, which recommends offering prolactin measurement in children and young people (CYP) with signs or symptoms of hyperprolactinemia 1. Key considerations for the investigation of suspected hyperprolactinemia include:

• Measuring serum prolactin levels, with the understanding that levels can vary by age and sex, and that reference ranges should be age-specific and sex-specific 1
• Considering the potential for stress and prolactin pulsatility to affect serum prolactin levels, and thus potentially requiring serial measurements over time to confirm elevated levels 1
• Assessing for confounding conditions such as hypothyroidism, renal and/or hepatic impairment, and use of medications that cause hyperprolactinemia, as these can impact serum prolactin levels 1
• Evaluating for macroprolactinemia, a condition where macroprolactin (a complex of prolactin and IgG antibody) is present in the blood, which can cause falsely elevated serum prolactin levels, particularly in asymptomatic individuals 1 Additional investigations that may be necessary include:
• Thyroid function tests (TSH, free T4) to rule out hypothyroidism as a cause of elevated prolactin levels
• Renal function and liver function tests to assess for potential organ impairment that could impact prolactin levels
• Pregnancy test in women of childbearing age, as pregnancy can cause hyperprolactinemia
• Pituitary function tests (LH, FSH, testosterone in men, estradiol in women, IGF-1, and morning cortisol) to assess for other hormonal abnormalities
• Magnetic resonance imaging (MRI) of the pituitary with contrast to identify potential pituitary adenomas or other lesions, particularly in cases with very high prolactin levels or symptoms suggestive of a mass effect 1.

From the Research

Investigations for Suspected Hyperprolactinemia

To diagnose and manage hyperprolactinemia effectively, several investigations should be conducted. These include:

• Serum Prolactin Measurement: The initial step in diagnosing hyperprolactinemia is to measure the serum prolactin level 2. It's essential to ensure that the sample is drawn in the morning with the patient in a fasting state, as prolactin levels can fluctuate throughout the day 3.
• Repeat Prolactin Measurement: If the initial prolactin level is elevated, it should be repeated to confirm the result, as transient elevations can occur due to various factors such as stress or sleep 3.
• Medical History and Physical Examination: A thorough medical history and physical examination are crucial to identify any underlying causes of hyperprolactinemia, such as pregnancy, primary hypothyroidism, or the use of certain medications 4, 3.
• Laboratory Tests: Additional laboratory tests may be necessary to rule out other causes of hyperprolactinemia, including thyroid function tests and renal function tests 4, 3.
• Macroprolactin Screening: Macroprolactinemia is a common cause of hyperprolactinemia, and screening for macroprolactin should be considered, especially if the prolactin level is elevated without an obvious cause 4, 2.
• Pituitary Magnetic Resonance Imaging (MRI): If the prolactin level is significantly elevated (>250 ng/mL) or if there are symptoms suggestive of a pituitary mass, pituitary MRI should be performed to evaluate for a prolactinoma or other sellar masses 4.
• Assessment of Anterior Pituitary Function: Evaluation of anterior pituitary function may be necessary, especially if there are symptoms of hypogonadism or other hormonal deficiencies 5.

Special Considerations

• Hook Effect: In cases of large pituitary adenomas, the "hook effect" can lead to falsely low prolactin levels, which can be unmasked by repeating the prolactin measurement after serum dilution 4.
• Polyethylene Glycol (PEG) Precipitation: Measurement of prolactin post-PEG precipitation can help identify macroprolactinemia, which may interfere with prolactin assays 2.