What are the symptoms and effects of elevated prolactin levels?

Elevated Prolactin: Symptoms and Effects

Elevated prolactin causes hypogonadism through inhibition of hypothalamic kisspeptin and gonadotropin secretion, resulting in reproductive dysfunction, sexual symptoms, galactorrhea, and potential long-term complications including osteoporosis. 1

Primary Clinical Manifestations

Reproductive and Sexual Effects

Women experience:

• Menstrual irregularities including oligomenorrhea and amenorrhea 2, 1
• Infertility due to anovulation 2, 3
• Galactorrhea (inappropriate breast milk production), which develops in a significant proportion of affected women 1

Men experience:

• Decreased libido and erectile dysfunction 1, 4
• Hypogonadism with profoundly low testosterone levels 2
• Gynecomastia in some cases 1, 5
• Infertility 2, 4

Tumor Mass Effects (When Caused by Prolactinomas)

• Visual field defects occur when macroadenomas compress the optic chiasm, though resolution is achieved in 67% of patients treated with dopamine agonists 1
• Headaches are commonly reported, particularly with larger tumors 1
• Pituitary apoplexy can occur rarely with large tumors 1
• Delayed or arrested puberty in younger patients 2

Long-Term Complications

• Osteoporosis and osteopenia result from prolonged hypogonadism 3, 4
• Bone density disturbances occur due to chronic sex hormone deficiency 4

Common Etiologies to Consider

Pathological Causes

Prolactinomas are the most common pathological cause of chronic hyperprolactinemia, with prolactin levels usually exceeding 4,000 mU/L in children and adolescents and correlating with tumor size 1, 5

Medication-Induced Hyperprolactinemia

Antipsychotics are the most frequent medication cause, acting through dopamine antagonism 2, 1, 6

• Typical antipsychotics and risperidone are most commonly implicated 7
• Other medications include antidepressants (particularly SSRIs), antihypertensives, prokinetics, and H2-receptor antagonists 1, 6, 7

Secondary Causes

• Primary hypothyroidism causes hyperprolactinemia in 43% of women and 40% of men, likely due to compensatory TRH hypersecretion 1
• Chronic kidney disease is associated with hyperprolactinemia in 30-65% of adult patients due to increased secretion and reduced renal clearance 1
• Severe liver disease 1
• Pituitary stalk compression by mass lesions interrupts inhibitory dopaminergic tone 1

Critical Diagnostic Pitfalls

Macroprolactinemia

10-40% of patients with elevated prolactin have macroprolactinemia, a benign condition with biologically inactive prolactin complexes 2, 1

• Among adults with macroprolactinemia, 20% still have galactorrhea, 45% have oligo-amenorrhea, and 20% have pituitary adenomas, indicating some may have concurrent true hyperprolactinemia 1
• Assessment should be performed in cases of mild or incidental elevation, especially in asymptomatic patients 2, 1

The "Hook Effect"

Approximately 5% of patients with macroprolactinomas show paradoxically normal or mildly elevated prolactin due to assay saturation at very high concentrations 2, 1

• Serial serum dilutions should be requested when large pituitary lesions show unexpectedly low prolactin levels 2, 1

Stress-Related Elevation

Stress can elevate prolactin levels up to five times the upper limit of normal 1

• For modestly elevated levels, serial measurements 20-60 minutes apart using an indwelling cannula help differentiate stress-related from organic disease 2

Treatment Considerations

Dopamine agonists are first-line treatment for prolactinomas to reduce serum prolactin and induce tumor shrinkage 2

• Cabergoline is preferred over bromocriptine due to superior effectiveness and better tolerability 2
• Treatment normalizes prolactin levels, restores gonadal function, and reduces tumor size in the vast majority of patients 4, 8