PRL

**Physiology** - Source: lactotrophs (acidophils) of the anterior pituitary. Physiologic hyperplasia occurs in pregnancy. - Actions: promotes breast development and milk PRODUCTION (not ejection; oxytocin mediates let-down). Inhibits GnRH release, which suppresses LH/FSH, ovulation, and spermatogenesis. This is why breastfeeding causes lactational amenorrhea and reduced fertility. - Regulation: - Dopamine from the tuberoinfundibular pathway (hypothalamus) acts on D2 receptors and INHIBITS PRL. This is the main control. PRL is the only anterior pituitary hormone with dominant negative regulation. - Stimulators: TRH, estrogen (pregnancy), breastfeeding/nipple stimulation, sleep, stress, exercise. - PRL provides negative feedback by increasing hypothalamic dopamine turnover. - Signaling: cytokine (JAK/STAT) receptor pathway. - Estrogen in pregnancy raises PRL, but high estrogen/progesterone block its milk-producing action at the breast. Milk production starts after delivery when these hormones fall.

**Causes of hyperprolactinemia** - Physiologic: pregnancy, lactation, nipple stimulation, stress, sleep. - Pathologic: - Prolactinoma: the most common functional pituitary adenoma. Microadenomas (<10 mm) are more common in women. Macroadenomas are more common in men, who often present late with mass effect. - Stalk effect: any mass or injury compressing the pituitary stalk reduces dopamine delivery, so PRL rises mildly (usually <100 ng/mL). - Drugs (dopamine antagonists or depleters): antipsychotics (risperidone and haloperidol are most prominent), metoclopramide, domperidone, methyldopa, reserpine. Also verapamil, estrogens, and some SSRIs. - Primary hypothyroidism: high TRH stimulates PRL. - Renal failure (reduced clearance) and cirrhosis. - Macroprolactinemia (an inactive PRL complex) is a lab pitfall. - Hook effect: with a very large prolactinoma, the assay can show a falsely low PRL. Diluting the sample reveals the true value.

**Clinical features** - Women: secondary amenorrhea or oligomenorrhea, galactorrhea, infertility, vaginal dryness, low bone density from hypoestrogenism. - Men: decreased libido, erectile dysfunction, infertility, gynecomastia, rarely galactorrhea. - Mass effect from macroadenomas: headache and bitemporal hemianopsia (optic chiasm compression), and possible hypopituitarism.

**Diagnosis** - Measure serum PRL. First rule out pregnancy, hypothyroidism (TSH), renal disease, and medications. - PRL >200 ng/mL strongly suggests a prolactinoma. Levels correlate with tumor size. - MRI of the pituitary if the cause is not found.

**Treatment** - First line: dopamine agonists, cabergoline (preferred, better tolerated and more effective) or bromocriptine (preferred in pregnancy attempts). These shrink the tumor and normalize PRL. - Side effects: nausea, orthostatic hypotension. At high doses, cabergoline carries a risk of cardiac valve fibrosis (5-HT2B agonism). - Surgery (transsphenoidal resection) for resistant tumors or intolerance to medication. Radiation is rarely used. - If a drug is the cause, stop or switch it (for example, to aripiprazole, a partial D2 agonist, which can lower PRL).

**Related: low PRL** - Sheehan syndrome (postpartum pituitary necrosis) presents with failure to lactate and is often the first sign.

**High-yield pearls** - Dopamine inhibits PRL, so dopamine antagonists raise it and dopamine agonists lower it. - Prolactinoma is the most common functional pituitary adenoma. Histology shows a chromophobic or acidophilic adenoma, and psammoma bodies can appear. - Do not confuse PRL (prolactin) with PRL as an abbreviation for "plasma renin level" or other uses. In USMLE context it almost always means prolactin.