Workup of hyperprolactinemia

Measurement of serum prolactin should be performed only when clinically indicated

Normal prolactin levels are less than 25 μg/L in females and less than 20 μg/L in males.¹ Measurement is indicated for erectile or ejaculatory dysfunction, amenorrhea, oligomenorrhea, infertility, low libido, or galactorrhea outside pregnancy or nursing.¹ The prevalence of hyperprolactinemia in adult populations ranges from 0.4% to 17% in people with amenorrhea, oligomenorrhea, or abnormal uterine bleeding.² Causes of hyperprolactinemia include macroprolactinemia, pregnancy, medications (dopaminergic antagonists, neuroleptics, antiemetics), untreated primary hypothyroidism, liver failure, renal failure, and hypothalamic or pituitary diseases.¹

Mild asymptomatic hyperprolactinemia (20–200 μg/L) is common and often spurious

People with asymptomatic, mild hyperprolactinemia should undergo repeat prolactin measurement in 2–4 weeks, testing for macroprolactin, and testing to exclude pregnancy with a serum β human chorionic gonadotropin.^1,3 Macroprolactinemia results from a larger biologically inactive isoform of prolactin that causes mild hyperprolactinemia but is not clinically important; detection may prevent further unnecessary investigations.¹ Neuroimaging for asymptomatic patients should be avoided, to reduce unnecessary health care costs and burden of incidental or clinically insignificant findings.⁴ Appendix 1 (available at www.cmaj.ca/lookup/doi/10.1503/cmaj.241710/tab-related-content) shows an algorithm for the workup of hyperprolactinemia.

Antipsychotic medication can cause marked prolactin elevation

Symptomatic hyperprolactinemia is commonly associated with use of antipsychotics (incidence of 18%–93%).⁵ First-generation antipsychotics, as well as risperidone, paliperidone, and amisulpride, can cause elevation in prolactin (> 100 μg/L).¹ Some second-generation antipsychotics cause milder hyperprolactinemia (< 100 μg/L).¹ Hyperprolactinemia secondary to antipsychotic use is often indiscernible from other causes; consultation with an endocrinology specialist for workup and management is appropriate.

Marked hyperprolactinemia (> 200 μg/L) in the absence of interfering medications is suggestive of prolactinoma

This scenario should prompt further evaluation for hypopituitarism and visual dysfunction with referral to an endocrinology specialist.^1,3 Prolactinomas are associated with hyperprolactinemia proportional to size (i.e., 100–200 μg/L for < 1 cm, to > 10 000 μg/L for > 3 cm).^1,3

Hyperprolactinemia accompanied by visual dysfunction (extraocular movement dysfunction, field deficit, or decreased acuity) is an indication for urgent neuroimaging and assessment by an ophthalmologist

Although gadolinium-enhanced magnetic resonance imaging (MRI) of the sella is gold standard,¹ contrast-enhanced computed tomography of the sella is appropriate if MRI is not immediately available. A pituitary macroadenoma contacting the optic chiasm requires urgent consultation with endocrinology and neurosurgery specialists.

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