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Prolactin


Definition


  • Prolactin is a single-chain polypeptide composed of 198 amino acids and is secreted by the anterior cells of the pituitary gland. Prolactin secretion is controlled by the hypothalamus primarily through the release of prolactin-inhibiting factor (dopamine) and prolactin-releasing factor (serotonin). TRH stimulates prolactin secretion and is useful as a provocative test to evaluate prolactin reserves and abnormal secretion of prolactin by the pituitary. The primary physiologic function of prolactin is to stimulate and maintain lactation in women.
  • Normal range:
    • Males: 2.64 " “13.13 Ž ¼g/L
    • Females <50 years (premenopausal): 3.34 " “26.72 Ž ¼g/L
    • Females >50 years (postmenopausal): 2.74 " “19.64 Ž ¼g/L

Use


  • Aiding in evaluation of pituitary tumors, amenorrhea, galactorrhea, infertility, and hypogonadism
  • Monitoring therapy of prolactin-producing tumors

Interpretation


Increased In


  • Amenorrhea/galactorrhea
    • 10 " “25% of women with galactorrhea and normal menses
    • 10 " “15% of women with amenorrhea without galactorrhea
    • 75% of women with both galactorrhea and amenorrhea/oligomenorrhea
    • Cause of 15 " “30% of cases of amenorrhea in young women
  • Pituitary lesions (e.g., prolactinoma, section of pituitary stalk, empty sella syndrome, 20 " “40% of patients with acromegaly, ≤80% of patients with chromophobe adenomas); concentrations are usually >200 ng/mL.
  • Hypothalamic lesions (e.g., sarcoidosis, eosinophilic granuloma, histiocytosis X, TB, glioma, craniopharyngioma); concentrations are usually >200 ng/mL.
  • Other endocrine diseases:
    • Approximately 20% of cases of hypothyroidism (second most common cause of hyperprolactinemia). Therefore, serum TSH and T4 should always be measured.
    • Addison disease
    • Polycystic ovaries
    • Glucocorticoid excess " ”normal or moderately elevated prolactin
  • Ectopic production of prolactin (e.g., bronchogenic carcinoma, renal cell carcinoma, ovarian teratomas, acute myeloid leukemia)
  • Children with sexual precocity " ”may be increased into pubertal range
  • Neurogenic causes (e.g., nursing and breast stimulation, spinal cord lesions, chest wall lesions such as herpes zoster)
  • Stress (e.g., surgery, hypoglycemia, vigorous exercise, seizures)
  • Pregnancy (increases to 8 " “20 times normal by delivery, returns to normal 2 " “4 weeks postpartum unless nursing occurs)
  • Lactation
  • Chronic renal failure (20 " “40% of cases; becomes normal after successful renal transplant but not after hemodialysis)
  • Liver failure (due to decreased prolactin clearance)
  • Idiopathic causes (some probably represent early cases of microadenoma too small to be detected by CT scan)
    • Drugs " ”most common cause; usually subsides a few weeks after cessation of using drug; these concentrations are usually 20 " “100 ng/mL
      • Neuroleptics (e.g., phenothiazines, thioxanthenes, butyrophenones)
      • Antipsychotic drugs (e.g., Compazine, Thorazine, Stelazine, Mellaril, Haldol)
      • Dopamine antagonists (e.g., metoclopramide, sulpiride)
      • Opiates (morphine, methadone)
      • Reserpine
      • Alpha-methyldopa (Aldomet)
      • Estrogens and oral contraceptives
      • Thyrotropin-releasing hormone
      • Amphetamines
      • Isoniazid

Decreased In


  • Hypopituitarism: postpartum pituitary necrosis (Sheehan syndrome), idiopathic hypogonadotropic hypogonadism
  • Drugs
    • Dopamine agonists
    • Ergot derivatives (bromocriptine mesylate, lisuride hydrogen maleate)
    • Levodopa, apomorphine, clonidine

Limitations


  • Normal prolactin secretion varies with time, which results in serum prolactin levels two to three times higher at night than during the day.
  • The biologic half-life of prolactin is approximately 20 " “50 minutes. Serum prolactin levels during the menstrual cycle are variable and commonly exhibit slight elevations during the mid-cycle.
  • Prolactin levels in normal individuals tend to rise in response to physiologic stimuli including sleep, exercise, nipple stimulation, sexual intercourse, hypoglycemia, pregnancy, and surgical stress.
  • Prolactin values that exceed the reference values may be due to macroprolactin (prolactin bound to immunoglobulin). Macroprolactin should be evaluated if signs and symptoms of hyperprolactinemia are absent or pituitary imaging studies are not informative.
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