Hyperprolactinemia Causes

Aka: Hyperprolactinemia Causes, Galactorrhea Causes

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II. Causes: Timing of increases

  1. Very brief increases in Prolactin (hours)
    1. Meals
    2. Clozapine
    3. Generalized Tonic-Clonic Seizure
    4. Sexual intercourse
  2. Transient increase in Prolactin levels (days to weeks)
    1. First-generation Antipsychotic Medications (e.g. Haloperidol)
    2. Second-generation Antipsychotic Medications (except Clozapine)
    3. Recent Alcohol or Nicotine use
  3. Sustained increase in Prolactin levels (weeks to months)
    1. Exogenous Estrogen
    2. Pregnancy
    3. Lactation
    4. Narcotics
    5. Chronic Renal Failure
    6. Cirrhosis
    7. Prolactinoma
  4. References
    1. Naus (2009) Federal Practitioner p. 44-9
    2. Haddad (2001) J Psychopharmacol 15(4):293-5 [PubMed]

III. Causes: Physiologic

  1. Breast stimulation
  2. Sexual Intercourse
  3. Eating or Dehydration
  4. Exercise
  5. Sleep
  6. Stress
  7. Lactation
  8. Pregnancy or Puerperium
    1. Prolactin levels may reach 200 mcg/L
    2. Resolves within 6 months postpartum
    3. Galactorrhea considered unrelated to pregnancy at >12 months postpartum (and after cessation of Breast Feeding)
  9. Neonatal Galactorrhea (Witch's Milk)
    1. Resolves in first 2 months of life

IV. Causes: Medications

  1. See Medication Causes of Hyperprolactinemia

V. Causes: Non-Neoplastic

  1. Afferent Neural Stimulation
    1. Mechanism
      1. Chest wall Sensory Nerve signal passed via spinal cord to Hypothalamus
      2. Signal reduces Dopamine levels, which in turn generate less inhibition of Prolactin secretion
    2. Breast
      1. Chronic Breast Abscess
      2. Excessive nipple or Breast manipulation
        1. Irritating clothes
        2. Ill-fitting brassieres
        3. Nipple rings
    3. Chest Wall and Skin
      1. Herpes Zoster
      2. Mastectomy or other Breast surgery
      3. Thoracotomy
      4. Burn Injury
    4. Spinal Cord tumor, injury or surgery
      1. Syringomyelia
      2. Tabes Dorsalis
  2. Endocrine
    1. Adrenal Adenoma or tumor
    2. Adrenal Insufficiency
    3. Hypothyroidism (related to TRH increase)
    4. Ovarian tumor
    5. Polycystic Ovary Disease
    6. FSH-Secreting Tumor (related to Estrogen increase)
  3. Prolactin Inhibiting Factor (PIF) synthesis Inhibition
    1. Hypothalamic cause
    2. Cerebrovascular Accident (Infarction)
    3. Infiltrative Disease
      1. Encephalitis or post-Encephalitis
      2. Hemochromatosis
      3. Histiocytosis
      4. Sarcoidosis
      5. Tuberculosis
      6. Schistosomiasis
      7. Schuller-Christian Disease
    4. Neuroaxis Irradiation (Radiation Therapy)
    5. Pseudocyesis
    6. Parkinson's Disease
  4. Prolactin Inhibiting Factor (PIF) transport interrupted
    1. Pituitary stalk section interrupted
    2. Pituitary Stalk compression
      1. Cerebral Aneurysm
      2. Cerebral cyst
      3. Empty sella syndrome
      4. Pseudotumor Cerebri
      5. Rathke's Cleft Cyst
  5. Other non-neoplastic causes
    1. Acute Intermittent porphyria
    2. Hepatic Cirrhosis
    3. Multiple Sclerosis
    4. Chronic Kidney Disease (Chronic Renal Failure or Renal Insufficiency)
      1. Prolactin levels may reach 1000 mcg/L

VI. Causes: Neoplastic

  1. Hypothalamic Dopamine (Prolactin Inhibiting Factor or PIF) deficiency
    1. Hypothalamic Dopamine synthesis inhibition
      1. Hypothalamic Tumors
        1. Craniopharyngioma
        2. Germinoma
        3. Meningioma
        4. Metastases
      2. Pineal Tumors (Primary or metastatic)
    2. Pituitary stalk compression (hypothalamic Dopamine transport interrupted)
      1. Hypothalamic tumor
      2. Pituitary tumor
  2. Prolactin-Secreting tumors
    1. Pituitary tumors
      1. Pituitary Adenoma (Prolactinoma)
        1. ProlactinSecreting tumors represent 40% of pituitary Secreting tumors
      2. Acromegaly
        1. Pituitary Adenomas Secreting Growth Hormone also secrete Prolactin in up to 50% of cases
        2. Growth Hormone also has an independent Lactation effect
      3. Cushing's Disease
      4. Nelson Syndrome (ACTH-Secreting Pituitary Adenoma)
        1. Follows adrenalectomy for Cushing Disease
    2. Ectopic tumor production
      1. Breast Cancer
      2. Bronchogenic Carcinoma
      3. Hypernephroma
  3. Other tumors
    1. Hydatidiform Mole

VII. References

  1. Stenchever (2001) Comprehensive Gynecology, p. 1125-42
  2. Bruehlman (2022) Am Fam Physician 106(6): 695-700 [PubMed]
  3. Samperi (2019) J Clin Med 8(12):2203 +PMID: 31847209 [PubMed]
  4. Serri (2003) CMAJ 169:575-81 [PubMed]

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