What are the possible causes of elevated prolactin in a 36-year-old woman?

Causes of Elevated Prolactin in a 36-Year-Old Woman

Elevated prolactin in a 36-year-old woman is most commonly caused by medications (especially dopamine antagonists), prolactinomas, primary hypothyroidism, or macroprolactinemia—each requiring systematic exclusion before pursuing further evaluation. 1, 2

Systematic Approach to Etiology

1. Medication-Induced Hyperprolactinemia (Most Common Reversible Cause)

• Antipsychotic medications are the leading pharmacological cause, particularly typical antipsychotics and risperidone among atypicals, which directly antagonize dopamine's inhibitory effect on prolactin secretion 1, 3, 4
• Antidepressants with serotonergic activity (SSRIs, MAO inhibitors, some tricyclics) frequently elevate prolactin 3, 4
• Antihypertensive agents, prokinetics (metoclopramide, prochlorperazine), H2-receptor antagonists, and opiates are additional common culprits 1, 3, 4
• Medication-induced hyperprolactinemia typically produces levels below 100 ng/mL (2,000 mU/L), though rare cases with combination therapy can reach higher levels 5

2. Prolactinomas (Most Common Pathological Cause)

• Prolactin-secreting pituitary adenomas are the most frequent pathological cause of chronic hyperprolactinemia 1, 6
• Prolactin levels correlate directly with tumor size: microprolactinomas typically produce modest elevations, while levels >100 ng/mL (>2,000 mU/L) strongly suggest a prolactinoma 2, 6
• Women typically present earlier than men with menstrual irregularities (oligomenorrhea, amenorrhea), galactorrhea, and infertility due to gonadotropin suppression 1, 6, 7
• Macroprolactinomas may additionally cause headaches and visual field defects from optic chiasm compression 1, 6

3. Primary Hypothyroidism

• Hypothyroidism causes hyperprolactinemia in 43% of women with frank disease and 36% with subclinical disease, mediated by compensatory thyrotropin-releasing hormone (TRH) hypersecretion 1, 6
• Thyroid dysfunction can produce pituitary hyperplasia that mimics a true prolactinoma on imaging 6
• Always measure TSH and free T4 before attributing hyperprolactinemia to a pituitary adenoma 1, 2

4. Macroprolactinemia (Common Benign Mimic)

• Macroprolactinemia accounts for 10–40% of all hyperprolactinemia cases and represents biologically inactive prolactin-immunoglobulin complexes 1, 2, 6
• Patients are typically asymptomatic, though 20% may have galactorrhea, 45% oligomenorrhea, and 20% coexist with true pituitary adenomas 6
• Routine macroprolactin analysis is mandatory for mildly or incidentally elevated prolactin, especially in asymptomatic individuals 2, 6

5. Pituitary Stalk Compression ("Stalk Effect")

• Non-functioning pituitary masses or other sellar/parasellar lesions can compress the pituitary stalk, interrupting dopamine delivery and causing mild-to-moderate prolactin elevation 6
• Prolactin levels with stalk compression typically remain <100 ng/mL (<2,000 mU/L), distinguishing this from true prolactinomas 6

6. Chronic Kidney Disease and Severe Liver Disease

• Chronic kidney disease causes hyperprolactinemia in 30–65% of adult patients through increased prolactin secretion and reduced renal clearance 1, 6
• Severe liver disease is also associated with elevated prolactin 1, 6

7. Physiological and Stress-Related Causes

• Pregnancy and lactation are the most important physiological causes to exclude in reproductive-age women 7, 8
• Stress, nipple stimulation, sexual activity, chest wall trauma, and sleep can transiently elevate prolactin up to 5 times the upper limit of normal 6, 8
• For modestly elevated levels, repeat measurement with 2–3 samples drawn 20–60 minutes apart via indwelling cannula helps differentiate stress-related from organic hyperprolactinemia 1, 2

Critical Diagnostic Pitfalls to Avoid

The "Hook Effect"

• In patients with large pituitary masses but paradoxically normal or mildly elevated prolactin, request serial dilutions of the serum sample 1, 2, 6
• This assay artifact occurs in approximately 5% of macroprolactinomas when extremely high prolactin concentrations saturate the immunoassay, producing falsely low results 1, 2

Timing and Interpretation

• A single blood sample at any time of day is sufficient for initial assessment; fasting and morning timing are not mandatory 1, 2
• Use age- and sex-specific reference ranges; typical upper limits for non-pregnant adult women are approximately 20 ng/mL (425 mU/L) 1, 6

Clinical Consequences of Hyperprolactinemia

• Prolactin suppresses hypothalamic kisspeptin, inhibiting gonadotropin-releasing hormone (GnRH) and causing hypogonadotropic hypogonadism 6
• This manifests as anovulation, menstrual disturbances, infertility, decreased libido, and galactorrhea in women 1, 6, 7
• Chronic hypogonadism increases risk of osteoporosis and other long-term complications 7