What is the appropriate workup and management for a patient with hyperprolactinemia (elevated prolactin levels)?

From the Guidelines

The workup for hyperprolactinemia should begin with a single blood sample collected at any time of day to measure prolactin levels, as recommended by the most recent guidelines 1. This approach is supported by high-quality evidence and allows for the identification of hyperprolactinemia, which can be caused by various factors including pituitary adenomas, hypothyroidism, renal and hepatic impairment, and certain medications. Key considerations in the workup include:

• Confirming the elevation with repeat testing to rule out physiologic causes like stress and prolactin pulsatility 1
• Ruling out physiologic causes like pregnancy, breastfeeding, and medication effects (antipsychotics, metoclopramide, verapamil)
• Laboratory evaluation including thyroid function tests to exclude hypothyroidism, renal and liver function tests, and assessment for symptoms of hypogonadism
• Magnetic resonance imaging (MRI) of the pituitary to identify potential prolactinomas or other sellar masses Management depends on the underlying cause and clinical presentation, with dopamine agonists being first-line therapy for prolactinomas. Cabergoline is the preferred dopamine agonist due to its superior effectiveness and lower adverse effect profile, as supported by moderate-quality evidence 1. Treatment goals include normalizing prolactin levels, restoring gonadal function, reducing tumor size, and alleviating symptoms like galactorrhea and visual disturbances. Regular monitoring includes prolactin levels every 1-3 months initially, then every 6-12 months once stable, with follow-up MRIs at 3-6 months after treatment initiation and then annually until stable. In cases of resistance or intolerance to medical therapy, surgery or radiotherapy may be considered, with careful multidisciplinary discussion and consideration of the patient's preferences and adherence to treatment. Overall, the management of hyperprolactinemia requires a comprehensive approach that takes into account the underlying cause, clinical presentation, and patient preferences, with the goal of improving morbidity, mortality, and quality of life. Key points to consider in management include:
• Graduated dose increments of cabergoline for patients resistant to standard doses 1
• Consideration of surgery or radiotherapy for patients with resistance or intolerance to medical therapy, or those with acute complications like apoplexy or severe visual impairment 1

From the FDA Drug Label

Since hyperprolactinemia with amenorrhea/galactorrhea and infertility has been found in patients with pituitary tumors, a complete evaluation of the pituitary is indicated before treatment with bromocriptine mesylate. The appropriate workup for a patient with hyperprolactinemia (elevated prolactin levels) includes:

• A complete evaluation of the pituitary to rule out pituitary tumors
• Assessment of symptoms such as amenorrhea, galactorrhea, and infertility
• Laboratory tests to measure prolactin levels and other hormone levels as needed
• Imaging studies such as MRI or CT scans to evaluate the pituitary gland and rule out other potential causes of hyperprolactinemia 2 Management of hyperprolactinemia may involve:
• Medications such as dopamine agonists (e.g. bromocriptine, cabergoline) to reduce prolactin levels
• Surgery to remove pituitary tumors if present
• Monitoring of prolactin levels and symptoms to adjust treatment as needed 3

From the Research

Diagnosis of Hyperprolactinemia

• Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis, and it can occur in both men and women, although it is more common in women 4.
• The diagnosis of hyperprolactinemia involves measuring serum prolactin levels, which should be done in the morning with the patient in a fasting state 5.
• A single elevated prolactin level is not diagnostic, and a repeat level should be obtained to confirm the diagnosis 5.
• The medical history and laboratory tests can help eliminate common physiologic and pharmacologic causes of hyperprolactinemia, such as pregnancy, primary hypothyroidism, and treatment with certain drugs 5.

Radiologic Imaging

• Radiologic imaging of the sella turcica is necessary to establish whether a prolactin-secreting pituitary adenoma or other lesion is present 5.
• Imaging with computerized tomography (CT) and magnetic resonance imaging (MRI) can help define the presence of a lesion compatible with a pituitary tumor 6.

Treatment of Hyperprolactinemia

• The treatment of hyperprolactinemia usually involves medical therapy with dopamine agonist drugs, such as bromocriptine and cabergoline 6, 4.
• Bromocriptine is a semisynthetic ergot alkaloid that directly stimulates specific pituitary cell membrane dopamine D2 receptors and inhibits prolactin synthesis and secretion 6.
• Cabergoline has a long duration of action and is given once or twice weekly, and it is clearly superior to bromocriptine in efficacy and tolerability 4.
• Surgery is reserved for patients with tumors that do not respond to medical therapy or have a large cystic component, or for patients who cannot tolerate dopamine agonists or experience pituitary apoplexy 5.

Management of Dopamine Agonist-Resistant Prolactinoma

• Dopamine agonist resistance is characterized by failure to achieve normoprolactinemia and a 30% or more reduction in maximal tumor diameter under maximally tolerated doses 7.
• The management of drug-resistant prolactinomas includes switching to cabergoline, dose escalation of cabergoline, transsphenoidal neurosurgery, radiotherapy, and temozolomide for malignant/aggressive prolactinomas 7.
• Echocardiographic monitoring is advised in patients taking high doses of cabergoline due to the potential association with cardiac valvular fibrosis 7.