What is the evaluation and management approach for a patient with hyperprolactinemia?

Evaluation of Raised Prolactin

Confirm hyperprolactinemia with a repeat fasting morning measurement, systematically exclude secondary causes (medications, hypothyroidism, pregnancy, renal/hepatic disease), assess for macroprolactinemia in mild elevations, and obtain pituitary MRI when prolactin is significantly elevated or when testosterone is <150 ng/dL with low-normal LH. 1

Initial Confirmation and Timing

• Repeat prolactin measurement preferably in the morning while fasting to exclude stress-induced or pulsatile elevation 1
• For modestly elevated levels, consider serial measurements 20-60 minutes apart using an indwelling cannula to differentiate stress-related hyperprolactinemia from organic disease 1, 2
• Stress alone can elevate prolactin up to five times the upper limit of normal 3

Systematic Exclusion of Secondary Causes

Medication Review

• Review all medications that antagonize dopamine, particularly antipsychotics and antiemetics (like prochlorperazine), as these are among the most common causes of hyperprolactinemia 1, 3

Laboratory Screening

• Screen for pregnancy in all women of reproductive age 1
• Measure TSH to exclude primary hypothyroidism, which causes hyperprolactinemia in 43% of women and 40% of men with overt hypothyroidism 3
• Assess renal function, as chronic kidney disease causes hyperprolactinemia in 30-65% of adult patients 3
• Evaluate liver function in patients with suspected severe liver disease 3

Assessment for Macroprolactinemia

• Screen for macroprolactinemia in patients with mildly or incidentally elevated prolactin levels, especially if asymptomatic, as it accounts for 10-40% of all hyperprolactinemia cases 1, 3, 4
• Macroprolactinemia represents biologically inactive prolactin complexes, though 20% still have galactorrhea, 45% have oligo-amenorrhea, and 20% have pituitary adenomas 3

Hormone Panel Assessment

• Measure LH levels in all patients with confirmed hyperprolactinemia to help establish etiology 1, 2
• Measure testosterone in men, particularly if symptoms of hypogonadism are present 1
• Evaluate IGF-1 levels to rule out mixed prolactin and growth hormone hypersecretion 1
• In men with breast symptoms or gynecomastia, measure estradiol 1

Clinical Symptom Assessment

Evaluate for specific manifestations of hyperprolactinemia:

In Women

• Menstrual irregularities, oligomenorrhea, or amenorrhea 1, 5
• Galactorrhea (inappropriate breast milk production) 3, 5
• Infertility and anovulation 1, 5
• Decreased libido 5

In Men

• Decreased libido and erectile dysfunction 3, 5
• Infertility 1
• Gynecomastia 5

Mass Effect Symptoms

• Visual field disturbances suggesting optic chiasm compression 1
• Headaches, particularly with larger tumors 3
• Delayed or arrested puberty in younger patients 1

Pituitary Imaging

Indications for MRI

• Obtain pituitary MRI when prolactin levels are significantly elevated (typically >4,000 mU/L or 188 μg/L), suggesting a prolactinoma 1, 2
• Perform MRI regardless of prolactin level in patients with visual symptoms or signs of mass effect 2
• Consider MRI in men with total testosterone <150 ng/dL combined with low/low-normal LH 1
• MRI is indicated even with mild prolactin elevations when unexplained, as pituitary adenomas can present with only modestly elevated prolactin 2

Critical Diagnostic Pitfalls to Avoid

The "Hook Effect"

• Request serial dilutions (1:100 dilution) for prolactin measurement in patients with large pituitary lesions (≥3 cm) but paradoxically normal or only mildly elevated prolactin levels 1, 3, 4
• This assay artifact occurs in approximately 5% of macroprolactinomas due to assay saturation at very high concentrations 3, 4

Prolactin Level Interpretation

• Prolactin >250 ng/mL is highly suggestive of prolactinomas and virtually excludes non-functioning pituitary adenomas 4
• Prolactin <100 ng/mL is typical for drug-induced hyperprolactinemia, macroprolactinemia, or stalk compression, though up to 25% of microprolactinomas or cystic macroprolactinomas may also present with these levels 4

Referral Indications

• Refer to endocrinology for persistently elevated prolactin levels of unknown etiology after excluding common causes 1
• Refer men with total testosterone <150 ng/dL and low/low-normal LH 1

Treatment Approach Once Diagnosis Established

First-Line Medical Therapy

• Dopamine agonists are first-line treatment for prolactinomas to reduce serum prolactin and induce tumor shrinkage 1
• Cabergoline is preferred over bromocriptine due to superior effectiveness (given once or twice weekly vs. daily) and better tolerability 1, 6, 7

Monitoring During Treatment

• Monitor prolactin levels to assess treatment response 1, 2
• For macroprolactinomas, repeat MRI 3-6 months after starting treatment 1
• For microprolactinomas, re-imaging depends on clinical and biochemical follow-up 1

Important Safety Considerations with Dopamine Agonists

Cabergoline-specific warnings 8:

• All patients require baseline cardiovascular evaluation including echocardiogram to assess for valvular disease
• Use the lowest effective dose and periodically reassess need for continuing therapy
• Echocardiographic monitoring every 6-12 months is recommended during treatment
• Discontinue if new valvular regurgitation, restriction, or leaflet thickening develops
• Monitor for pleural, pericardial, and retroperitoneal fibrosis

Bromocriptine-specific warnings 9:

• Withdraw when pregnancy is diagnosed in patients treated for hyperprolactinemia
• Monitor blood pressure, particularly during first weeks of therapy
• Not recommended for prevention of physiological lactation or in patients with uncontrolled hypertension
• Monitor for pleural/pulmonary fibrosis and retroperitoneal fibrosis with long-term, high-dose treatment

Special Consideration: Fertility and Pregnancy

• Do not initiate testosterone therapy until prolactinoma is excluded or treated, as it does not address underlying pituitary pathology 1
• If fertility is desired, reproductive health evaluation is mandatory before treatment, including FSH and semen analysis 1
• Testosterone therapy would suppress spermatogenesis and should be avoided if fertility preservation is a goal 1