Hyperprolactinemia

Introduction

• Description: Hyperprolactinemia is the pathologic elevation of serum prolactin levels. The finding of elevated levels of prolactin is nonspecific with respect to the cause, thereby requiring careful clinical evaluation.

• Prevalence: Uncommon; reports vary from 1% to 30%, depending on the population studied.

• Predominant Age: Reproductive age.

• Genetics: No genetic pattern. A germline loss-of-function mutation in the prolactin receptor gene ( PRLR ) has been reported.

Etiology and Pathogenesis

• Causes: Prolactin is secreted solely by the lactotroph cells of the pituitary gland. Pituitary adenoma (most common). Pharmacologic—most often those that affect dopamine or serotonin: major tranquilizers (phenothiazines), trifluoperazine (Stelazine), and haloperidol (Haldol); some antipsychotic medications; metoclopramide (Reglan); less often, α-methyldopa and reserpine. Other—herpes zoster, chest wall/breast stimulation or irritation, physiologic during pregnancy, or after childbirth and/or breastfeeding.

• Risk Factors: Exposure to known pharmacologic agents, specific disease processes ( Table 194.1 ).

  Table 194.1

  Sources of Elevated Prolactin Levels

  Pharmacologic (Examples)	Pathophysiologic Causes
  Anesthetics	Central nervous system
  Central nervous system: dopamine-depleting agents	Cavernous sinus thrombosisInfection
  α-Methyldopa	Neurofibromas
  Monoamine oxidase inhibitors	Temporal arteritisTumors and cysts (all types)
  Reserpine	Hypothalamic
  Dopamine receptor blocking agents	CraniopharyngiomaGlioma
  Domperidone	Granulomas
  Haloperidol	Histiocytosis disease
  Metoclopramide	Sarcoid
  Phenothiazines	Tuberculosis
  Pimozide	Irradiation damage
  Sulpiride	Pituitary stalk transaction
  Dopamine reuptake blockers	SurgicalTraumatic
  Nomifensine	Pseudocyesis (functional)
  Histamine H 2 -receptor antagonists	Pituitary lesionsAcromegaly
  Cimetidine	Mixed growth hormone or
  Hormones	adrenocorticotropic hormone–
  Estrogens	prolactin-secreting adenoma
  Oral contraceptives	Prolactinoma
  Thyrotropin-releasing hormone	Somatic sourcesBreast augmentation or reduction
  Opiates	Bronchogenic carcinoma
  Stimulators of serotoninergic inhibitors	Chest wall traumaChronic nipple stimulation
  Amphetamines	Cushing’s syndrome
  Hallucinogens	Herpes zoster
  	Hypernephroma
  	Hypothyroidism
  	Pregnancy
  	Renal failure
  	Upper abdominal surgery

Signs and Symptoms

• Asymptomatic

• Bilateral, spontaneous milky discharge from both breasts (75%)

• Amenorrhea (30%)

• Large adenoma, clinical symptoms of impingement on the optic nerve or adjacent structures

• Fertility may be impaired even without menstrual cycle disruption

Diagnostic Approach