Galactorrhea and Hyperprolactinemia

Introduction


Galactorrhea is defined as nonpuerperal watery or milky breast secretion that contains neither pus nor blood. This secretion may be manifested spontaneously but may be detected after breast and nipple palpation. To detect galactorrhea, the breast examination should include compression of the glands from the periphery of the breasts toward the nipple concentrically. Confirmation of the diagnosis is through observation of microscopic fat globules in the expressed fluid. The incidence of this condition among reproductive-aged women is unknown but has been estimated to occur in 20–25% of women at some time in their life. Galactorrhea with amenorrhea is commonly associated with a pituitary adenoma.


Normal lactation


During pregnancy, the ductal system and lobules of the breast are primed by a multitude of hormones including estrogen, growth hormone, progesterone, insulin, thyroid hormone, glucocorticoids and human placental lactogen. The high levels of estrogen and progesterone that occur during pregnancy, however, block the action of prolactin and prevent milk production. Following delivery, the precipitous fall in these hormones in the presence of elevated prolactin levels results in lactation. Suckling stimulates the release of prolactin and oxytocin as well as thyroid-releasing hormone. The contraceptive effect of lactation is dependent on the intensity and frequency of suckling. Basal levels of prolactin can remain elevated for several months following weaning.


Pathophysiology


Prolactin (PRL), the critical hormone regulating puerperal-related lactation, is often involved in the physiology of galactorrhea. Normally, the anterior pituitary secretes prolactin at a low basal rate as a result of constant suppression by prolactin-inhibiting factor. Dopamine, the main component of prolactin-inhibiting factor, is secreted by the hypothalamus and delivered to the anterior pituitary via the portal system. Excessive secretion of PRL by anterior pituitary cells called lactotrophs results in hyperprolactinemia. A common cause of hyperprolactinemia is an adenoma, often referred to as a prolactinoma. The most common systemic disease resulting in galactorrehea is hypothyroidism. Low levels of thyroid hormone stimulate increased release of thyrotropin-releasing hormone which increases prolactin secretion. Other common causes include excessive breast manipulation, certain medications, and idiopathic (Box 91.1).


Since the predominant control of PRL release from the anterior pituitary is mediated by prolactin-inhibiting factor (PIF), any mechanical compression of the pituitary stalk or destructive process involving the pituitary gland or hypothalamus can interfere with tonic PIF inhibitory action and result in hyperprolactinemia and galactorrhea. Dopamine receptor antagonists, such as phenothiazines, directly inhibit dopamine action. Natural processes such as stress, sleep, nipple stimulation, pregnancy, and exercise also stimulate PRL release. Chronic renal failure may result in galactorrhea due to decreased clearance of prolactin through the kidneys. Some nonpituitary malignancies such as bronchogenic carcinoma or T-cell lymphomas may release prolactin.


Clinical presentation


Two easily recognizable consequences of elevated PRL in women are galactorrhea and menstrual cycle disturbances. Menstrual irregularities associated with hyperprolactinemia include amenorrhea, oligomenorrhea, luteal phase defects, and delayed menarche. Hyperprolactinemia may be associated with infertility, decreased libido and vaginal dryness or osteopenia (due to low estrogen levels). Changes in menstrual function are often the result of diminished hypothalamic pulsatile gonadotropin-releasing hormone secretion (GnRH) due to changes in hypothalamic dopamine activity, resulting in abnormal follicle-stimulating hormone/luteinizing hormone (FSH/LH) secretion. A direct inhibitory action of PRL on ovarian folliculogenesis and corpus luteum function is reported.



Box 91.1 Causes of hyperprolactinemia


Idiopathic (common cause)


Physiologic



  • hypothyroidism
  • early morning/sleep
  • high-protein meal
  • physical exercise
  • psychologic stress
  • late follicular phase or menstrual cycle or mid-cycle
  • suckling/pregnancy
  • coitus
  • exercise
  • breast manipulation
  • dehydration
  • “witch’s milk” in neonates

Hypothalamic-pituitary diseases



  • lactotroph hyperplasia
  • prolactinoma, micro- or macro-
  • Cushing’s disease
  • pituitary stalk compression or resection
  • empty sella syndrome
  • infiltrative, destructive or neoplastic diseases
  • craniopharyngiomas, sarcoidosis, tuberculosis, schistosomiasis
  • encephalitis
  • radiation
  • acromegaly
  • pseudotumor cerebri
  • hypothalamic cyst

Drugs


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Jun 6, 2016 | Posted by in GYNECOLOGY | Comments Off on Galactorrhea and Hyperprolactinemia

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