What is the cause of mildly elevated prolactin (hyperprolactinemia)?

From the Guidelines

Mildly elevated prolactin levels are most commonly caused by macroprolactin, a form of prolactin with low biological activity, and it is essential to assess baseline macroprolactin levels in such cases. According to the consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence, part 2, specific diseases 1, macroprolactin can be present in 10-40% of individuals with hyperprolactinemia. Other causes of mildly elevated prolactin include certain medications, such as antipsychotics and antidepressants, hypothyroidism, stress, and physiological factors like pregnancy and breastfeeding.

Some key points to consider when investigating mildly elevated prolactin levels include:

• Ruling out medication effects, stress, and physiological causes before considering pituitary disorders 1
• Assessing baseline macroprolactin levels to determine the presence of macroprolactinemia 1
• Considering the role of hypothyroidism, renal and hepatic impairment, and other confounding conditions in causing hyperprolactinemia 1
• Using age-specific and sex-specific prolactin reference ranges to diagnose hyperprolactinemia in children and adolescents 1

It is crucial to approach the diagnosis of mildly elevated prolactin levels with a comprehensive evaluation, considering various potential causes and using appropriate diagnostic tools to determine the underlying cause. A thorough investigation, including the assessment of macroprolactin levels and the exclusion of confounding conditions, is necessary to provide an accurate diagnosis and appropriate management.

From the FDA Drug Label

As with other drugs that antagonize dopamine D2 receptors, RISPERIDONE elevates prolactin levels and the elevation persists during chronic administration. RISPERIDONE is associated with higher levels of prolactin elevation than other antipsychotic agents. The cause of mildly elevated prolactin is likely Risperidone treatment due to its dopamine D2 receptor antagonism properties, which can lead to hyperprolactinemia 2.

• Key points:
  • Risperidone elevates prolactin levels
  • Elevation persists during chronic administration
  • Risperidone is associated with higher levels of prolactin elevation than other antipsychotic agents
  • Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion 2.

From the Research

Causes of Mildly Elevated Prolactin

• Physiologic causes:
  • Pregnancy 3, 4
  • Lactation 3, 4
  • Sleep-associated 5
  • Nipple stimulation and sexual orgasm 5
  • Chest wall stimulation or trauma 5
• Pathologic causes:
  • Prolactinoma (a type of pituitary tumor) 3, 6, 4
  • Primary hypothyroidism 3
  • Drug-induced hyperprolactinemia (e.g., antipsychotic drugs like risperidone) 3, 7
• Other causes:
  • Stress-induced hyperprolactinemia 5

Diagnosis and Treatment

• A careful history and examination, followed by laboratory tests and diagnostic imaging of the sella turcica, are necessary to determine the cause of hyperprolactinemia 3, 4
• Dopamine agonists (e.g., cabergoline, bromocriptine) are the primary treatment for hyperprolactinemia 3, 6, 4
• Surgery may be an alternative treatment option in certain circumstances 3, 6, 4