What is a Prolactinoma?
A prolactinoma is a benign prolactin-secreting pituitary adenoma that represents the most common type of pituitary tumor and the most frequent pathological cause of chronic hyperprolactinemia. 1, 2
Epidemiology & Tumor Characteristics
Prolactinomas show a 3–4.5-fold female predominance, with women typically presenting with microprolactinomas (<10 mm) and men more commonly presenting with larger, invasive macroadenomas (≥10 mm). 1, 2
In pediatric populations, 93% of prolactinomas are diagnosed after age 12, indicating typical adolescent presentation. 1
Giant prolactinomas (>40 mm) occur more frequently in children and adolescents than in adults. 1
These tumors are almost exclusively benign, though rare aggressive variants exist. 3
Clinical Features
Women Present Earlier with Hypogonadal Symptoms:
- Primary or secondary amenorrhea and oligomenorrhea are the most common presenting symptoms in females. 1
- Galactorrhea (inappropriate breast milk production) develops in a significant proportion of affected women. 1
- Infertility due to anovulation. 1
- Delayed or arrested puberty in adolescent girls. 1
Men Present Later with Mass-Effect Symptoms:
- Visual field defects occur in 73% of giant prolactinoma cases due to optic chiasm compression. 1
- Headaches occur in roughly half of patients with macroadenomas. 1
- Decreased libido and erectile dysfunction from hypogonadotropic hypogonadism. 1
- Gynecomastia secondary to hypogonadism. 1
- Delayed or arrested puberty in adolescent boys. 1
Mechanism of Hypogonadism:
- Prolactin suppresses hypothalamic kisspeptin, which inhibits gonadotropin secretion, leading to hypogonadotropic hypogonadism in both sexes. 1
Diagnostic Workup
Step 1: Measure Serum Prolactin
- A single prolactin measurement at any time of day is sufficient for initial assessment. 4, 5
- For modestly elevated levels, repeat sampling on a different day to exclude stress-related elevation (stress can elevate prolactin up to 5× the upper limit of normal). 1, 5
- Prolactin levels typically correlate with tumor size: levels >4,000 mU/L (approximately >200 ng/mL) strongly suggest a prolactinoma in children and adolescents. 1
Step 2: Exclude Secondary Causes Before Imaging
- Review all medications, particularly dopamine antagonists (antipsychotics, antiemetics), which are among the most common causes of hyperprolactinemia. 1, 4
- Screen for primary hypothyroidism (present in 43% of women and 40% of men with frank hypothyroidism). 1
- Assess for chronic kidney disease (hyperprolactinemia in 30–65% of adults) and severe liver disease. 1
- Screen for macroprolactinemia when prolactin is mildly or incidentally elevated, as it accounts for 10–40% of all hyperprolactinemia cases and represents biologically inactive prolactin complexes. 1, 4
Step 3: Pituitary MRI with and Without Contrast
- High-resolution pituitary MRI is the gold-standard imaging modality to define tumor size, invasiveness, and relationship to the optic chiasm. 1
- Obtain MRI when prolactin levels are significantly elevated or when visual symptoms or signs of mass effect are present. 5
Critical Diagnostic Pitfall: The "Hook Effect"
- In approximately 5% of macroprolactinomas, extremely high prolactin concentrations saturate the immunoassay, producing falsely low or normal measurements. 1, 6
- When a large pituitary mass is found on MRI but prolactin seems paradoxically normal or only mildly elevated, request manual serial dilutions of the serum sample to unmask true prolactin levels. 1, 4
Step 4: Assess Remaining Pituitary Function
- Measure LH, FSH, testosterone (in men), estradiol (in women), thyroid function, cortisol, and IGF-1 to identify concurrent hypopituitarism. 1, 5
- Visual field testing should be performed if a macroadenoma is found, as compression of the optic chiasm can occur. 4
Management
First-Line: Dopamine Agonist Therapy
- Cabergoline is the first-line medical treatment for prolactinomas, normalizing prolactin in up to 85% of patients and causing tumor shrinkage in up to 80%. 4, 7
- Cabergoline is superior to bromocriptine in effectiveness and tolerability. 4
- Visual field defects resolve in 67% of patients treated with dopamine agonists. 1
- Treatment goals: normalize prolactin levels, restore gonadal function, shrink tumor, and resolve mass effects. 8, 3
Important Caveats About Medical Therapy:
- Dopamine agonists are suppressive but not tumoricidal, so therapeutic effect is maintained only as long as the drug is administered. 8
- In most cases, treatment must be continued life-long, though one-third of patients may achieve definitive cure and permit treatment discontinuation. 2
- Pregnancy and menopause may promote spontaneous prolactin decline and anticipate cabergoline discontinuation in women. 2
- Side effects include orthostatic hypotension, nausea, and vomiting. 8
Second-Line: Transsphenoidal Surgery
- Main indications for surgery are intolerance of medication and tumors not responding to dopamine agonists. 8
- Primary surgical resection of microprolactinomas and enclosed macroprolactinomas performed by experienced pituitary neurosurgeons have similar remission rates to cabergoline (82% remission in microprolactinomas with initial prolactin <200 ng/mL). 8, 7
- Surgery should be strongly considered as primary therapy in microprolactinomas, non-invasive macroprolactinomas, or prior to attempting pregnancy. 7
Third-Line: Multimodality Therapy for Aggressive Tumors
- Aggressive prolactinomas and metastatic pituitary tumors should receive high-dose cabergoline, surgery, stereotactic radiosurgery (where suitable), and temozolomide. 7
- Evidence of resistance to cabergoline in invasive and proliferative tumors may indicate biological aggressiveness requiring alternative approaches. 2
Predictors of Treatment Success
- Higher baseline testosterone levels in men predict greater likelihood of spontaneous recovery of normal testosterone production after prolactin normalization. 1
- Preservation of other pituitary hormone secretion predicts successful restoration of the hypothalamic-pituitary-gonadal axis following treatment. 1