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Prolactin

A single chain polypeptide hormone secreted by specialize pituitary cells.

Has a major role in promoting postpartum lactation in women, and its role in men remains unclear.

Elevated levels are associated with decreased estradiol concentrations and anovulation.

Increased concentration of circulating prolactin associated with increased breast cancer risk.

Nurses Health Study of 850 patients revealed postmenopausal women in the top versus the bottom fourth of prolactin levels had a 30% increased risk of breast cancer, with an 80% increased risk for estrogen receptor/progesterone receptor positive tumors.

Primary hypothalamic control is inhibitory through the action of dopamine.

Hypothalamus influences production via 1 or more inhibitory factors that reach the pituitary via the hypothalamic/pituitary portal vessels.

Prolactin secretion is continuously inhibited by dopamine of hypothalamic origin, acting on pituitary cells known as lactotrophs.

With a disruption of the pituitary stalk a moderate increase in prolactin secretion occurs and decreased secretion of other pituitary hormones.

Hyperprolactinemic levels seen in pituitary adenomas, pregnancy, nipple stimulation, and as a response to stress.

Hyperprolactinemia lifetime prevalence is 90 per 100,000 women and 20 per 100,000 men.

Hyperprolactinemia may occur as a result of excess prolactin secretion, which can be caused by interruption of dopamine’s action.

Mild hyperprolactinemia is nonspecific:etiologies include primary hypothyroidism and medications.

When prolactin levels exceed 200 mcg/mL usually indicates the presence of the prolactinoma or growth hormone co-secreting pituitary tumor in the absence of renal insufficiency.

Prolactin level greater than 500 µg/mL are diagnostic of macro prolactinomas.

Hyperprolactinemia is caused mainly by pregnancy, prolactinomas, medications, chest wall injury, functional or mechanical interruption of the pituitary stalk dopamine transport. 

Prolactin levels are elevated in approximately 30% of patients with acromegaly.

Prolactin level should be measured in all patients with pituitary seller masses and hyperprolactinemia not explained by pregnancy or exposure to neuroleptic drugs should prompt pituitary imaging to rule out a pituitary mass.

Tumor size and magnitude of prolactin elevation in patients with prolactinomas correlate well, but not in patients with nonfunctioning pituitary adenomas.

Elevated levels can be seen with lactotroph hyperplasia when normal inhibition from dopamine is present as a result of traumatic damage to the dopaminergic neurons of the hypothalamus or pituitary stalk, or due to drugs that block dopamine receptors on lactotroph cells.

Suprasellar masses may disturb normal hypothalamus inhibition of prolactin secretion and cause hyperprolactinemia (stalk effect).

A mild level of hyperprolactinemia may be related to the stalk effect and not to a prolactinoma.

Elevated levels, hyperprolactinemia, may be seen with dopamine receptor antagonists such as phenothiazines, haloperidol, and domperidome.

Hyperprolactinemia can suppress the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, and suppresses the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and resulting in hypogonadism and low levels of the sex hormones estradiol and testosterone.

Hyperprolactinemia associated with estrogens, renal insufficiency, and hypothyroidism.

Hyperprolactinemia consequences include galactorrhea, hypogonadotropic hypogonadism with oligomenorrhea or amenorrhea in women and erectile dysfunction in men and impaired libido.

Hyperprolactinemia causes hypogonadism by decreasing pulsatile secretion of gonadotropin releasing hormone by the hypothalamus.

Differential diagnosis includes medication induced hyperprolactinemia and must be differentiated from prolactinomas, hypothalamic disease, hypothyroidism, and renal insufficiency.

Medications related to hyperprolactin levels include: phenothiazines, thioxanthines, butyrophenones, atypical antipsychotics, tricyclic and tetracyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, opiates, cocaine, verapamil, methyldopa, reserpine, metoclopramide domperidome, histamine2 receptor blockers and estrogens.

Antipsychotic, neuroleptic agents are the most common drugs associated with hyperprolactinemia as they are dopamine receptor blockers.

Thyrotropin releasing hormone rapidly increases release of prolactin.

Vasoactive intestinal peptide stimulates prolactin release.

Prolactin levels are frequently increased in sarcoidosis, between 3 and 32% of cases have hyperprolactinemia.

 

 

Prolactin level elevation frequently leads to amenorrhea, galactorrhea, or nonpuerperal mastitis in women with sarcoidosis.

Causes of hyperprolactinemia:

Physiological

pregnancy and pueperium

lactation

coitus

sleep exercise

stress

food consumption

Pituitary or Hypothalamus prolactin secreting pituitary adenomas

Acromegaly

Other sellar lesions interrupting dopamine inhibition

pituitary stalk disruption

radiation therapy

Seizures

Systemic

Medications: phenothiazines, haloperidol, risperidone, tricyclic antidepressants, metoclopromide, opioids, verapamil and others

Primary hypothyroidism

polycystic ovarian syndrome

Endstage renal disease

chronic liver disease

chest wall injury or lesion

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