6 days ago
Recognizing and Treating Hyperprolactinemia
In this podcast, I'm going to talk about hyperprolactinemia in primary care. Let's start with a case study. Hannah is a 32-year-old lady who presents to us in primary care with a 6-month history of a bilateral watery breast discharge. She has associated irregular periods. There's no family history of breast disease, breast cancer, or any other malignancy. Of note, past medical history includes a history of Graves disease treated with radioactive iodine. In terms of her social history, she lives with her partner and their 2-year-old daughter.
On examination, Hannah's breasts were symmetrical in appearance. There were no skin changes or no palpable mass in either breast. However, there was white discharge expressed from both breasts. There was no evidence of any local or distant lymphadenopathy. In terms of investigations, pregnancy test was negative, and her prolactin levels returned at 800 mIU/L. So, what is causing her high prolactin levels?
Let's start with a bit of background about prolactin. Prolactin is a peptide hormone produced in the anterior pituitary gland. The main physiologic role of prolactin is to initiate and sustain lactation. Prolactin also is responsible for the proliferation and differentiation of breast tissue during pregnancy.
Excessive production of prolactin can lead to subfertility and gonadal dysfunction due to suppression of gonadotropin-releasing hormone (GnRH) production from the hypothalamus. GnRH stimulates the pituitary gland to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which in turn stimulate the ovaries and testes to produce sex hormones.
Finally, dopamine inhibits prolactin production and helps regulate prolactin levels. Prolactin levels, of course, are high during pregnancy and lactation, but levels also increase after meals, exercise, stress, sleep, nipple stimulation, and any form of chest wall injury.
What are the pathologic causes of high prolactin levels? Causes include prolactin-secreting pituitary tumors or prolactinomas. Additionally, nonfunctioning or nonsecreting pituitary tumors can also lead to high prolactin levels, because they prevent the normal flow of dopamine to the pituitary gland due to compression of the pituitary stalk. Rarely, hypothalamic tumors might also be implicated, as can any form of head injury or seizure activity. A history of brain surgery or cranial radiotherapy can also lead to high prolactin levels. Other causes include kidney and liver failure and polycystic ovary syndrome.
Also, certain endocrine conditions can lead to high prolactin levels, including acromegaly and hypothyroidism. Hypothyroidism is, in fact, the cause of Hannah's symptoms. Her past radioactive iodine treatment for Graves disease has now rendered her hypothyroid, which has led to elevated prolactin levels.
Importantly, a range of medications we commonly prescribe in primary care can also lead to hyperprolactinemia: a range of antipsychotics, first-generation antipsychotics such as chlorpromazine and haloperidol, and second-generation antipsychotics such as aripiprazole. Most antiemetics can also lead to high prolactin levels (such as metoclopramide, haloperidol, and prochlorperazine). But, incidentally, cyclizine does not lead to high prolactin levels. The combined oral contraceptive pill can lead to hyperprolactinemia, as can many antidepressants, verapamil, opiates, cimetidine, and illicit drugs, including cocaine. Finally, commonly prescribed drugs such as omeprazole and trimethoprim can also lead to high prolactin levels.
How does hyperprolactinemia present? In women, it often presents as Hannah presented, with galactorrhea and menstrual disturbance. Reduced fertility, reduced libido, acne, and hirsutism are also other presenting features. Men can also present with galactorrhea, though this is much less common. More commonly, men present with loss of libido, erectile dysfunction, and subfertility, and sometimes gynecomastia. Importantly, we must remember, both men and women can present with visual field defects: for example, a bitemporal hemianopia or a headache due to the mass effect of a pituitary macroadenoma. Furthermore, low bone mineral density and an increased risk for osteoporosis can also be associated with longstanding elevated prolactin levels.
With regard to investigations, we simply need to repeat prolactin levels in the first instance because the stress of venipuncture itself can increase prolactin levels. We need to exclude pregnancy as appropriate and, importantly, review current medications, taking into account the wide range of drugs that can increase prolactin levels, as I've already outlined. In terms of further bloodwork, consider ordering a thyroid-stimulating hormone test to check thyroid function, a urea and electrolytes test to check kidney function, and a liver blood test to exclude any sort of hepatic failure, and also consider checking sex hormones: FSH, LH, and testosterone levels.
When looking at those prolactin results, results of 500-700 mIU/L for females and 325-700 mIU/L for men are rarely pathological or clinically significant, which is a really useful take-home message for us in primary care. However, very high levels of prolactin, over 5000 mIU/L, are strongly suggestive of an underlying pituitary tumor. When other causes have been excluded, such as drug-induced causes, diagnosis is usually confirmed by a pituitary MRI scan.
In terms of management, the main principle of management of hyperprolactinemia is to identify and treat the underlying cause, if feasible. The goals of treatment are, of course, to relieve any symptoms if present, such as galactorrhea, in Hannah's case, to prevent complications from osteoporosis or pressure effects and to restore fertility and sexual function. Treatment will very much depend on the underlying cause and will be largely driven by our secondary care colleagues, our endocrinology colleagues, and our neurosurgery colleagues. Treatment can include the use of dopamine agonists (for example, cabergoline and bromocriptine) to help regulate prolactin levels, and surgical treatment might include transsphenoidal surgery.
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Kevin Fernando. Recognizing and Treating Hyperprolactinemia - Medscape - Jun 03, 2025.
