Endocrine Society Issues Guidelines for Management of Hyperprolactinemia

Laurie Barclay, MD

February 15, 2011

February 15, 2011 — The Endocrine Society has released a new clinical practice guideline for the diagnosis and treatment of patients with hyperprolactinemia. The new recommendations for management of elevated levels of the hormone prolactin, which is associated with infertility, low sex drive, and bone loss, are reported in the February issue of the Journal of Clinical Endocrinology & Metabolism.

The evidence-based strategies highlighted in the guidelines include assessment of the cause of hyperprolactinemia, which may include use of specific medications, renal failure, hypothyroidism, and pituitary and parasellar tumors in patients with symptomatic nonphysiologic hyperprolactinemia. Also covered are treatment of drug-induced hyperprolactinemia and of prolactinomas, and indications and adverse effects of drugs used to treat prolactinomas.

"People with high prolactin levels who have few or no symptoms and no demonstrable pituitary tumor may not need treatment, but infertile or pregnant patients, and individuals with bothersome symptoms require specialized treatment depending on the cause of their condition," said lead author Shlomo Melmed, MD, chair of the Clinical Guidelines Subcommittee of The Endocrine Society Task Force and dean at Cedars-Sinai Medical Center in Los Angeles, California, in a news release.

"This new Clinical Practice Guideline helps clinicians diagnose hyperprolactinemia, identify the most appropriate treatment and manage prolactinomas in non-pregnant and pregnant individuals."

The Task Force of Endocrine Society–appointed experts, a methodologist, and a medical writer developed the evidence-based clinical practice guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations as well as the quality of the underlying evidence. Consensus was established through a single group meeting, several conference calls, and emails. Preliminary drafts of guidelines were reviewed and commented on by committees and members of The Endocrine Society, The European Society of Endocrinology, and The Pituitary Society.

Recommendations for Hyperprolactinemia

Specific recommendations for diagnosis of hyperprolactinemia include the following:

  • A single measurement of serum prolactin level can confirm the diagnosis if the level is above the upper limit of normal and the serum sample was obtained without excessive venipuncture stress. Dynamic testing of prolactin secretion is not recommended to diagnose hyperprolactinemia.

  • Macroprolactin evaluation is recommended in patients with asymptomatic hyperprolactinemia.

  • When there is a discrepancy between a very large pituitary tumor and a mildly elevated prolactin level, serial dilution of serum samples is recommended to eliminate the "hook effect," or an artifact that can occur with some immunoradiometric assays leading to a falsely low prolactin value.

Recommendations for Drug-Induced Hyperprolactinemia

Specific recommendations for management of drug-induced hyperprolactinemia are as follows:

  • In a symptomatic patient with suspected medication-induced hyperprolactinemia, the drug should be discontinued for 3 days or an alternative drug substituted, and the serum prolactin measurement should then be repeated. However, the patient's physician should be consulted before an antipsychotic agent is discontinued or substituted. If the drug cannot be discontinued and the onset of the hyperprolactinemia does not coincide with starting therapy, magnetic resonance imaging (MRI) of the pituitary gland may distinguish medication-induced hyperprolactinemia from symptomatic hyperprolactinemia caused by a pituitary or hypothalamic mass.

  • Patients with asymptomatic medication-induced hyperprolactinemia should not be treated. Estrogen or testosterone can be used in patients with long-term hypogonadism (hypogonadal symptoms or low bone mass) caused by medication-induced hyperprolactinemia.

  • If it is not possible to stop the drug causing medication-induced hyperprolactinemia, cautious administration of a dopamine agonist should be considered, in consultation with the patient's physician.

Recommendations for Prolactinoma

Specific recommendations for management of prolactinoma are as follows:

  • Dopamine agonist therapy is recommended to reduce prolactin levels and tumor size and to restore gonadal function in patients with symptomatic prolactin-secreting microadenomas or macroadenomas. Compared with other dopamine agonists, cabergoline is more effective in normalizing prolactin levels and in shrinking pituitary tumors.

  • Dopamine agonists are not recommended for asymptomatic patients with microprolactinomas. However, patients with microadenomas who have amenorrhea can be treated with a dopamine agonist or oral contraceptives.

  • In patients treated with dopamine agonists for at least 2 years who no longer have elevated serum prolactin levels or visible tumor on MRI, careful clinical and biochemical follow-up therapy may be tapered and perhaps discontinued.

Recommendations for Resistant, Malignant Prolactinoma

Specific recommendations for management of resistant and malignant prolactinoma are as follows:

  • For symptomatic patients in whom normal prolactin levels are not achieved or who have significant shrinking of the tumor size while receiving standard doses of a dopamine agonist, the dose should be increased rather than referring the patient for surgery.

  • Patients resistant to bromocriptine should be switched to cabergoline.

  • Symptomatic patients with prolactinomas who cannot tolerate high doses of cabergoline or who are unresponsive to dopamine agonist therapy should be offered trans-sphenoidal surgery. Patients intolerant of oral bromocriptine may respond to intravaginal administration. Radiation therapy is recommended for patients in whom surgical treatment fails or for those with aggressive or malignant prolactinomas.

  • Temozolomide therapy is recommended for patients with malignant prolactinomas.

Recommendations for Pregnant Women With Prolactinoma

Specific recommendations for management of prolactinoma during pregnancy are as follows:

  • Women with prolactinomas should discontinue dopamine agonist therapy as soon as pregnancy is recognized, except for selected patients with invasive macroadenomas or adenomas abutting the optic chiasm.

  • Serum prolactin measurements should not be performed during pregnancy.

  • Unless there is clinical evidence for tumor growth, such as visual field impairment, routine use of pituitary MRI during pregnancy is not recommended in patients with microadenomas or intrasellar macroadenomas.

  • Women with macroprolactinomas that do not shrink during dopamine agonist therapy or women who cannot tolerate bromocriptine or cabergoline should be counseled regarding the potential benefits of surgical resection before attempting pregnancy.

  • Pregnant women with prolactinomas who experience severe headaches and/or visual field changes should have formal visual field assessment followed by MRI without gadolinium.

  • Bromocriptine therapy is recommended in patients who experience symptomatic growth of a prolactinoma during pregnancy.

The European Society of Endocrinology and The Pituitary Society cosponsored development of the clinical practice guidelines. Members of the task force have disclosed various financial relationships with Novartis, Ipsen, Pfizer, Novo Nordisk, Merck Serono, LG Life Sciences, and/or Teva. A complete description is available in the original article.

J Clin Endocrinol Metab. 2011;96:273-288. Full text

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