Prolactinoma

Risk factors

• Female sex (microadenomas), male sex (macroadenomas)
• Reproductive years (typical presentation)
• MEN1 (menin) — pituitary + parathyroid + pancreatic NET
• Familial isolated pituitary adenoma (AIP mutation)
• Drugs that elevate prolactin (must exclude before diagnosing tumor): antipsychotics (risperidone, haloperidol), metoclopramide, methyldopa, opioids, estrogens, verapamil
• Pregnancy (physiologic), chest wall stimulation

Pathophysiology

Prolactin secretion is tonically inhibited by hypothalamic dopamine. Lactotroph adenomas escape dopamine inhibition and secrete prolactin autonomously. Pituitary stalk compression by ANY large mass (non-prolactinoma adenoma, craniopharyngioma) can also raise prolactin by interrupting dopamine delivery (the 'stalk effect') — usually mild (<150 ng/mL). Hyperprolactinemia suppresses GnRH, producing hypogonadotropic hypogonadism.

Clinical presentation

Differential diagnosis

• Drug-induced hyperprolactinemia — Antipsychotics, antiemetics, opioids; review meds; stop or substitute if possible
• Primary hypothyroidism — TRH stimulates prolactin; check TSH; treat thyroid disease and recheck PRL
• Pregnancy and lactation — Physiologic; β-hCG
• Stalk-effect hyperprolactinemia from non-prolactinoma macroadenoma — PRL usually <150 ng/mL with large pituitary lesion; pituitary axis testing for other hormone excess/deficiency
• Chronic kidney disease, cirrhosis — Reduced clearance; check creatinine and LFTs
• Chest wall / nipple stimulation, herpes zoster — Reflex prolactin release
• Polycystic ovary syndrome — Oligomenorrhea, hirsutism; PRL normal or mildly elevated
• Macroprolactinemia (asymptomatic, lab artifact) — Big-big prolactin form; clinically irrelevant; PEG precipitation differentiates

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A["Galactorrhea / amenorrhea /<br/>hypogonadism / mass effect"] --> B["Serum prolactin<br/>+ TSH + β-hCG"]
  B --> C["Review meds<br/>(antipsychotics, antiemetics)"]
  C --> D{"PRL elevated and confirmed?"}
  D -->|No| E["Reassess other causes of symptoms"]
  D -->|"Yes, but asymptomatic"| P["PEG precipitation<br/>to exclude macroprolactin"]
  D -->|"Yes, symptomatic"| F["Pituitary MRI"]
  F --> G{"Adenoma?"}
  G -->|"Micro <10 mm + symptoms"| H["Cabergoline 0.25 mg 2x/week"]
  G -->|"Macro ≥10 mm"| Q{"PRL >150-200?"}
  Q -->|Yes| I["Cabergoline + visual fields<br/>+ pituitary axis workup"]
  Q -->|"No, only modest"| R["Repeat PRL on 1:100 dilution<br/>to exclude hook effect"]
  R -->|"High after dilution"| I
  R -->|"Still modest"| S["Stalk effect from<br/>non-prolactin-secreting mass"]
  G -->|"Empty / non-pituitary"| J["Reassess causes; PEG precipitation"]
  H --> K["Recheck PRL q1-3 mo"]
  I --> K
  K --> L{"Resistant or intolerant?"}
  L -->|Yes| M["Transsphenoidal surgery"]
  L -->|No| N["Continue DA; consider taper after 2-3 y of normal PRL and tumor regression"]

Treatment

Complications

• Infertility, hypogonadism, decreased libido, sexual dysfunction
• Osteoporosis from chronic hypogonadism
• Visual field loss (macroadenoma)
• Pituitary apoplexy (sudden hemorrhage/infarction of adenoma)
• Cardiac valvular fibrosis with high-dose long-term cabergoline (rare at typical prolactinoma doses, but echo recommended for cumulative dose monitoring)
• Impulse control disorders on dopamine agonist (gambling, hypersexuality)

PANCE pearls

• Dopamine agonists (cabergoline first-line) shrink prolactinomas — even macroadenomas — so SURGERY is rarely needed.
• Always check TSH, β-hCG, and review medications BEFORE diagnosing a prolactinoma.
• Mildly elevated prolactin (25-100) with a large pituitary mass = stalk effect OR hook effect — request a 1:100 diluted prolactin before labeling the mass non-functioning or referring for surgery.
• Macroprolactin (big-big prolactin, immunologically active but bioinactive) causes asymptomatic 'hyperprolactinemia' — confirm with PEG precipitation before workup.
• Hook effect: very high prolactin can give a falsely low immunoassay result — dilute the sample if you suspect a very large prolactinoma.
• Counsel patients about impulse control side effects of dopamine agonists (gambling, hypersexuality).

References

• Endocrine Society 2011 — Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline (Melmed et al., J Clin Endocrinol Metab 2011)
• Pituitary Society 2023 — Diagnosis and Management of Prolactin-Secreting Pituitary Adenomas: A Pituitary Society International Consensus Statement (Petersenn et al., Nat Rev Endocrinol 2023)
• AACE/ACE 2015 — AACE/ACE Disease State Clinical Review: Clinical Relevance of Macroprolactin in the Absence or Presence of True Hyperprolactinemia (Samson SL et al., Endocr Pract 2015;21(12):1427-1435)