Approach
Hyperprolactinemia in premenopausal women results in galactorrhea, menstrual irregularity, and infertility. Galactorrhea is less common in postmenopausal women due to estrogen deficiency. Men may also present with symptoms of secondary hypogonadism, such as reduced libido, impotence, and infertility. Later presentation in men and postmenopausal women means that these patients are more likely to present with locally invasive tumors which may compress adjacent structures in the suprasellar region (optic tracts or chiasm) or the parasellar cavernous sinuses (other cranial nerves), causing mass effect features (e.g., visual disturbances, ophthalmoplegia, headaches). Chronic hyperprolactinemia with subsequent secondary hypogonadism may lead to osteoporosis.
Hormonal determination
A single measurement of serum prolactin taken without significant venepuncture stress is sufficient to establish the diagnosis of hyperprolactinemia. In cases of mild hyperprolactinemia, it may be worth measuring several sequential prolactin measurements, separated by at least 20 minutes and taken via an indwelling catheter in order to minimise venepuncture stress. Secondary causes should be excluded by a careful history, examination, and pregnancy test. Mild prolactin level elevations, <100 micrograms/L (<2000 mIU/L), can occur with certain drugs, including typical and atypical antipsychotics (e.g., phenothiazines, risperidone, clozapine), opiates, antiemetics (e.g., metoclopramide, domperidone), estrogens, H2 blockers, and verapamil. Therefore it is important to take a full drug history.
Prolactin levels can be elevated in renal failure and in primary hypothyroidism, so renal and thyroid function should be checked prior to further investigating a raised prolactin level. Generally, prolactin levels associated with prolactinomas correspond with tumor size.[11] Most patients with a microprolactinoma will have a serum prolactin level between 100 and 200 micrograms/L (2000 and 4000 mIU/L), and a level of >250 micrograms/L (>5000 mIU/L) is almost certainly a macroprolactinoma.[12] In nonfunctioning pituitary adenomas, disconnection hyperprolactinemia can occur. This is where prolactin is raised due to pituitary stalk compression impeding dopamine transport via the portal vessels to the anterior pituitary. In this setting, serum prolactin is normally <100 micrograms/L (<2000 mIU/L).[12]
In cases of significant hyperprolactinemia, gonadotropins (follicle-stimulating hormone, luteinizing hormone) and estradiol/testosterone may be low, consistent with secondary hypogonadism. All patients, but particularly those with macroprolactinomas, should have assessment of the remainder of their pituitary function. Up to 50% of patients with growth hormone (GH)-secreting tumors causing acromegaly also have hyperprolactinemia.[11] Therefore it is important to exclude this condition in patients with an elevated prolactin using clinical assessment, and random GH and insulin-like growth factor 1 measurement.
Pituitary imaging
A gadolinium-enhanced magnetic resonance imaging is required to confirm the diagnosis of a prolactinoma. Computed tomography does not provide sufficient pituitary visualization.
Visual-field examination
Clinical visual-field examination is performed in all patients as part of the initial patient assessment. However, computerized visual field examination (perimetry) is also required in all patients with a macroadenoma with suprasellar extension to exclude the existence of optic chiasmal compression.
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