Hyperprolactinemia means abnormally high levels of prolactin (PRL) in the blood.
Normal PRL levels (may vary according to the lab):
- < 23.5–25 ng/mL or μg/L for non-pregnant women
- 80–400 ng/mL or μg/L for pregnant women
- < 20–21.5 ng/mL or μg/L for men
- Occurs in < 1% of the general population
- The most common form of pituitary hormone hypersecretion (hyperpituitarism) in both men and women
- Slightly more common in females
- Physiologic causes:
- Pregnancy (most common):
- During pregnancy, PRL levels rise but are regulated by estrogen and progesterone.
- After the birth, PRL levels will decrease without nipple stimulation.
- Nipple stimulation (via breastfeeding/suckling)
- Sleep (levels return to normal within an hour of awakening)
- Pregnancy (most common):
- Pathologic causes:
- PRL-secreting pituitary adenomas caused by a monoclonal expansion of the lactotrophs
- Approximately 50% of cases are due to the overexpression of pituitary tumor transforming gene (PTTG1) and MEN1 syndrome.
- Cause approximately 50% of non-pregnant cases
- Primary hypothyroidism: Low levels of thyroid hormones cause a compensatory increase in thyrotropin-releasing hormone (TRH), a PRL‑releasing hormone.
- Pharmacologic causes:
- Any drug that inhibits dopamine secretion or blocks dopamine receptors, because dopamine inhibits PRL secretion
- Most commonly, antidepressants and antipsychotics
- Disorders of the hypothalamus or hypothalamic-pituitary region: such as tumors of the hypothalamus (craniopharyngioma), head trauma, surgery, or non–PRL-secreting pituitary adenomas
- Chest-wall trauma: invokes the reflex suckling arc
- Chronic renal failure:
- Produces an increase in PRL levels through a decrease of urinary elimination of the hormone
- The uremic state will also stimulate the release of PRL.
PRL functions and effects
- Growth and development of mammary glands during pregnancy
- Production of breast milk
- Lactational amenorrhea (lack of menstruation during breastfeeding)
- A decrease in sexual drive and reproductive function
- Secreted by the anterior pituitary gland (lactotroph cells)
- Dopamine inhibits PRL secretion.
- TRH and estrogen stimulate PRL secretion.
- Also stimulated by sleep, exercise, pregnancy, and stress
- Increased levels of PRL inhibit gonadotropin-releasing hormone (GnRH) → decrease in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) → decreases estrogen → cessation of ovulation and menstruation
Excessive and prolonged increase in PRL levels → suppression of GnRH → lower levels of LH, FSH → chronically low estrogen and testosterone → hypogonadotropic hypogonadism
- Varies depending on the degree of increase and cause
- May be asymptomatic (especially in postmenopausal women)
- In men and premenopausal women, hyperprolactinemia presents as hypogonadism:
- Infertility due to the cessation of ovulation
- Amenorrhea (lack of menstruation) or irregular menstrual bleeding
- Galactorrhea (discharge of milk from nipples in men or non-breastfeeding women)
- Decrease in libido
- Erectile dysfunction and gynecomastia in men
- Large tumors can present with headaches and visual problems.
Diagnosis and Management
- Pregnancy testing to rule out pregnancy in premenopausal women
- Repeated measurements of PRL levels to confirm hyperprolactinemia (PRL level > 200 ng/ml in a man or non-pregnant woman → prolactinoma)
- TSH levels should be measured to rule out hypothyroidism (PRL < 100 ng/mL).
- Visual field testing to assess complications
- FSH, LH, testosterone, and estrogen levels will be decreased.
- Magnetic resonance imaging (MRI) is the study of choice to identify or confirm pituitary masses.
- Particularly useful in cases with a history of head trauma, headaches, and visual problems
- 1st-line: dopamine agonists to suppress PRL secretion
- The underlying cause should be addressed:
- Discontinuation of medication in drug-induced cases
- Surgery might be needed in the case of pituitary adenomas.
- Medical treatment of primary hypothyroidism
- Dialysis or renal transplant in the case of chronic renal failure
- If medical therapy fails, transsphenoidal surgery is needed with postoperative radiation.
- Small prolactinomas with minimal symptoms should be followed with serial PRL levels and computed tomography (CT)/MRI scans yearly.
The following conditions should be ruled out in the case of hyperprolactinemia:
- Hypothyroidism: deficiency of the T3 and T4 hormones. Will present with high levels of TSH and moderately increased PRL levels.
- Chronic renal failure: progressive loss of renal function. Will present with uremic syndrome in patients undergoing dialysis.
- Gigantism/acromegaly: excess production of growth hormone by the pituitary gland, due to a somatotroph adenoma. The tumor will produce an increase in PRL through the inhibition of regulation from the hypothalamus.
- Prolactinomas: tumors from the anterior pituitary that secrete PRL. Prolactinomas present with typical signs and symptoms of elevated PRL levels, with PRL usually over 200 ng/ml. An MRI identifies the location and size of the tumor.
- Pituitary adenomas: tumors that can secrete PRL or other pituitary hormones (growth hormone (GH) or adrenocorticotropic hormone (ACTH)). Pituitary adenomas can disrupt the hypothalamic-pituitary axis, affecting the inhibition of PRL release. An MRI will confirm the diagnosis.
- Kasper, Fauci, Hauser, Longo, Jameson, & Loscalzo. (2015). Harrison’s Principles of Internal Medicine (19th ed., pp. 2266-2267).
- Kumar, V., Abbas, A.K., & Aster, J. (2014). Robbins Basic Pathology (9th ed., pp. 719-720).