From the Guidelines
Mildly elevated prolactin levels are often caused by macroprolactin, a form of prolactin with low biological activity, and assessing baseline macroprolactin levels is recommended in cases of mildly or incidentally elevated serum prolactin. 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 hyperprolactinaemia. Other causes of mildly elevated prolactin include medications such as antipsychotics, certain antidepressants, metoclopramide, domperidone, and some antihypertensives like verapamil, as well as physiological causes like pregnancy, breastfeeding, nipple stimulation, stress, exercise, and sleep 1.
Some key points to consider when investigating mildly elevated prolactin levels include:
- Repeating the test while fasting and avoiding breast stimulation for 24 hours to rule out temporary increases in prolactin levels
- Reviewing medications and potentially adjusting them if they are suspected to be the cause of elevated prolactin
- Ruling out underlying conditions such as hypothyroidism, chronic kidney disease, liver cirrhosis, and polycystic ovary syndrome
- Considering the role of macroprolactin and assessing baseline macroprolactin levels in cases of mildly or incidentally elevated serum prolactin 1
- Using age-specific and sex-specific prolactin reference ranges and excluding confounding conditions such as hypothyroidism, renal and/or hepatic impairment, and use of medications that cause hyperprolactinaemia 1
It is essential to note that prolactin elevation can occur due to various factors, including increased dopamine or direct stimulation of prolactin release from the pituitary gland. If no clear cause is found and levels remain elevated, further evaluation with pituitary imaging may be warranted to rule out small prolactinomas. The diagnosis of hyperprolactinaemia in children and young people requires age-specific and sex-specific prolactin reference ranges and the exclusion of confounding conditions 1.
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 Risperidone treatment due to its dopamine D2 receptor antagonism properties 2.
From the Research
Causes of Mildly Elevated Prolactin
- Mildly elevated prolactin levels can be caused by various factors, including the intake of certain drugs, compression of the pituitary stalk by other pathology, hypothyroidism, renal failure, cirrhosis, chest wall lesions, or idiopathic hyperprolactinemia 3
- Physiologic causes of hyperprolactinemia include pregnancy, lactation, sleep-associated, nipple stimulation and sexual orgasm, chest wall stimulation, or trauma 4
- Stress is also an important physiologic cause of hyperprolactinemia, and its clinical significance is still being explored 4
- Antipsychotic drug therapy, such as risperidone, can be associated with endocrine abnormalities, including an increase in serum prolactin level due to a drug-induced benign pituitary tumor (prolactinoma) 5
Differential Diagnoses
- If serum prolactin levels are above 200 microg/L, a prolactin-secreting pituitary adenoma (prolactinoma) is the underlying cause 3
- If levels are lower, differential diagnoses should be considered, including the intake of various drugs, compression of the pituitary stalk by other pathology, hypothyroidism, renal failure, cirrhosis, chest wall lesions, or idiopathic hyperprolactinemia 3
- A thorough clinical evaluation, including medical history, physical examination, and laboratory tests, is necessary to determine the underlying cause of mildly elevated prolactin levels 6