🧠🧪 Prolactin

Prolactin is a peptide hormone produced by lactotroph cells in the anterior pituitary and plays a central role in lactation and reproductive regulation. Unlike most pituitary hormones, prolactin secretion is primarily under tonic inhibitory control by dopamine. In clinical practice, raised prolactin is a common incidental finding and requires careful interpretation to avoid over-investigation. Understanding its physiology helps distinguish benign, reversible causes from true pituitary pathology.

⚙️ Physiology and Regulation

Prolactin secretion is regulated mainly by hypothalamic dopamine acting via D2 receptors to suppress release. Reduction in dopamine tone (e.g. pituitary stalk compression, dopamine antagonists) leads to hyperprolactinaemia. Oestrogen stimulates lactotroph proliferation and prolactin synthesis, explaining physiological rises in pregnancy. Prolactin also inhibits gonadotropin-releasing hormone (GnRH), thereby suppressing LH and FSH and reducing fertility.

📊 Normal Prolactin Levels (Adults)

Prolactin reference ranges vary by laboratory assay, but the key difference is units: UK commonly reports mIU/L, while US commonly reports ng/mL. Use local lab ranges where possible.

🔄 Conversion (approximate): 1 ng/mL ≈ 21 mIU/L (and 1 mIU/L ≈ 0.048 ng/mL). ⚠️ Because assays differ, conversions are approximate — always interpret using your lab’s reference interval.

🧠 Clinical teaching pearl: Unit-mixups cause lots of false “abnormal” referrals. A prolactin of 25 ng/mL (US) can be normal in women, but 25 mIU/L (UK) would be unusually low. If mildly raised, repeat a rested morning sample and review drugs (antipsychotics, metoclopramide, SSRIs) before jumping to MRI.

⚠️ Ranges vary by laboratory and assay. Always interpret using local reference values.

🧠 Interpretation Principles

Prolactin is highly sensitive to stress, sleep, exercise, venepuncture anxiety, and illness. Mild elevations are frequently physiological or drug-related. Persistent elevation on repeat testing is more clinically meaningful than a single abnormal result. Macroprolactin should be excluded in asymptomatic patients with moderate elevation.

⚠️ Causes of Hyperprolactinaemia

• 🟢 Physiological
  • Pregnancy and breastfeeding
  • Sleep and stress
  • Exercise
• 🔵 Drug-Induced
  • Antipsychotics (risperidone, haloperidol)
  • SSRIs and TCAs
  • Metoclopramide, domperidone
  • Opiates
• 🟠 Pituitary / Structural
  • Prolactinoma (micro/macroadenoma)
  • Non-functioning pituitary adenoma (stalk effect)
  • Craniopharyngioma
• 🟣 Systemic / Endocrine
  • Primary hypothyroidism (↑ TRH)
  • Chronic kidney disease
  • Cirrhosis
  • Chest wall trauma

🔻 Causes of Low Prolactin (Rare)

• Hypopituitarism
• Sheehan’s syndrome
• Dopamine agonist excess
• Post-pituitary surgery/radiotherapy

🔍 Clinical Features of Hyperprolactinaemia

• 🚺 Women: amenorrhoea, oligomenorrhoea, galactorrhoea, infertility
• 🚹 Men: reduced libido, erectile dysfunction, infertility
• Both: fatigue, low mood, osteoporosis
• Macroadenoma: headaches, visual field defects

🧪 Investigation Strategy

• Repeat fasting morning prolactin
• Exclude pregnancy
• Medication review
• TSH and free T4 (exclude hypothyroidism)
• Renal and liver function
• Macroprolactin screen if asymptomatic
• Pituitary MRI if persistent elevation >1000 mIU/L or symptoms

📈🧪 Prolactin Level Guide — Interpretation (UK 🇬🇧 & US 🇺🇸)

This guide applies to fasting morning samples after excluding pregnancy and acute stress. Always interpret alongside symptoms, medications, and repeat testing.

🧠 Teaching Pearl
Prolactin rises due to loss of dopaminergic inhibition. Drug-induced hyperprolactinaemia and stalk compression usually remain <2000 mIU/L. Levels >2000–3000 mIU/L strongly suggest autonomous tumour secretion. Always repeat before imaging unless severe symptoms are present.

💊 Management

• 🟢 Treat Underlying Cause
  • Stop/switch causative drugs if possible
  • Treat hypothyroidism
  • Optimise renal/liver disease
• 💉 Dopamine Agonists (First Line)
  • Cabergoline (preferred)
  • Bromocriptine (alternative)
  • Reduce tumour size and normalise prolactin
• 🏥 Surgery / Radiotherapy
  • For resistant or intolerant cases
  • Visual compromise

🏥 UK Clinical Practice Notes

• Repeat testing before imaging is standard practice
• Macroprolactin screening avoids unnecessary MRI
• Cabergoline is first-line in most NHS trusts
• Long-term follow-up via endocrinology is recommended

🚨 Red Flags

• Visual field loss
• Severe headaches
• Very high prolactin (>5000 mIU/L)
• Rapid symptom progression
• Hypopituitarism features

📚 Key Learning Points

Hyperprolactinaemia is most often physiological or drug-related rather than tumour-related. Always repeat and contextualise results before escalating investigation. Prolactin suppresses the reproductive axis, explaining most clinical features. In UK practice, careful stepwise assessment prevents unnecessary imaging and long-term overtreatment.