Experts issue guidance for diagnosing, treating hyperprolactinemia
The Endocrine Society released its first-ever clinical guidelines for the diagnosis and treatment of patients with hyperprolactinemia.
Previously, a guideline for hyperprolactinemia was not developed because there are few prospective, controlled trials on the disease, according to Shlomo Melmed, MD, chair of the task force that wrote the guidelines. This was one challenge in developing the guidelines, he said.
Patients 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, Melmed said in a press release. This new clinical practice guideline helps clinicians diagnose hyperprolactinemia, identify the most appropriate treatments and manage prolactinomas in non-pregnant and pregnant individuals.
Hyperprolactinemia is characterized by abnormally high circulating levels of prolactin, and is usually caused by the use of certain medications or by prolactinomas. Melmed said that hyperprolactinemia is a common disorder that leads to infertility, low sex drive and osteoporosis in both men and women.
To diagnose hyperprolactinemia, the task force recommends a single measurement of serum prolactin, as long as the serum sample was obtained without excessive venipuncture. The experts also recommend against the use of dynamic testing of prolactin secretion for diagnosis.
A prolactin level greater than 500 mcg/L is diagnostic of a macroprolactinoma, the task force wrote. Although a prolactin level greater than 250 mcg/L usually indicates the presence of a prolactinoma, selected drugs, including risperidone and metoclopramide, may cause prolactin elevations above 200 mcg/L in patients without evidence of adenoma.
In addition to excluding medication use as a cause of hyperprolactinemia, the task force also recommends that renal failure, hypothyroidism and parasellar tumors be excluded as the cause in patients with symptomatic nonphysiological hyperprolactinemia.
A number of physiological states including pregnancy, breast-feeding, stress, exercise and sleep can cause prolactin elevation, as can medications, the task force wrote. In about one-third of patients with kidney disease, hyperprolactinemia develops because of decreased clearance and enhanced production of the hormone.
When medication-induced hyperprolactinemia is suspected, the task force recommends discontinuation of the medication for 3 days, or substituting an alternative drug. If the onset of hyperprolactinemia did not coincide with the initiation of the suspected medication, a pituitary MRI should be obtained to determine if a pituitary tumor is the cause. They also recommend that asymptomatic patients with medication-induced hyperprolactinemia are not treated.
Neuroleptics/antipsychotic agents are the [medications] most commonly causing hyperprolactinemia, the task force wrote. Among patients taking typical antipsychotics, 40% to 90% have hyperprolactinemia, as do 50% to 100% of patients on risperidone.
According to Melmed, who is dean of Cedars-Sinai Medical Center and an Endocrine Today Editorial Board member, the most important recommendation is to exclude medication as a cause of hyperprolactinemia, before ordering an expensive MRI to diagnose a possible pituitary tumor.
The list of drugs that can cause hyperprolactinemia is very extensive, Melmed told Endocrine Today. Some of these drugs can cause quite marked elevation of prolactin, which mimics the same elevation we encounter in patients with pituitary tumors.
For the management of prolactinoma, the task force recommends dopamine agonist therapy to lower prolactin levels, decrease tumor size and restore gonadal function patients with symptomatic prolactin-secreting microadenomas and macroadenomas. They particularly recommend using cabergoline because it has higher efficacy at normalizing prolactin levels and it shrinks pituitary tumors.
It is unclear why cabergoline is more effective than bromocriptine, but the greater efficacy may be explained by the fact that cabergoline has a higher affinity for dopamine receptor binding sites, the task force wrote. Because the incidence of unpleasant side effects is lower with cabergoline, drug compliance may be superior for this medication.
In patients with prolactinomas who are symptomatic and resistant to standard doses of the dopamine agonists, the task force recommends increasing the dose to the maximum tolerable dose before referral to surgery. For patients with malignant prolactinomas, temozolomide therapy is recommended.
One of the important recommendations of these guidelines is that treatment for prolactinomas should primarily be medical, and these patients should initially not be sent to surgery, Melmed said. Medications for treating prolactinomas are efficacious and safe.
Lastly, the guidelines offer recommendations for managing prolactinomas during pregnancy. Women with prolactinomas are advised to discontinue dopamine agonist therapy when they discover they are pregnant. They also recommend against measuring serum prolactin measurements during pregnancy, as these will invariably be elevated, and against routine pituitary MRI in patients with microadenomas or intrasellar macroadenomas during pregnancy. by Emily Shafer
For more information:
- Melmed S. J Clin Endocrinol Metab. 2011;96:273-288.
Disclosure: Dr. Melmed reports no relevant financial disclosures.