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General Reference ⬇

Nejm 2003;349:2035

Pathophys and Cause ⬆ ⬇

Cause:

Abnormal prolongation or initiation of prolactin production

1/3 are true primary hyperprolactinemia, over half of these are due to micro- or macroadenomas and empty sella syndrome (Ann IM 1986;105:238); the rest are idiopathic including Argonz-Del Castillo syndrome (spontaneous), and postpregnancy (Chiari-Frommel syndrome)

2/3 are secondary types, from: hypothyroidism; renal failure; cirrhosis; hypothalamic disease; and medications like reserpine, phenothiazines, verapamil (Ann IM 1981;95:66), metoclopramide (Ann IM 1983;98:86), and cimetidine (Nejm 1982;306:26)

Pathophys:Hypothyroidism causes the syndrome because TRH itself causes prolactin release. Prolactin inhibits LH secretion and peak, thereby inhibiting menses

Signs and Symptoms ⬆ ⬇

Sx:

in women: amenorrhea (90%) and infertility; may be masked by bc pill use, and therefore present only as galactorrhea; galactorrhea or elicitable lactation

In males, galactorrhea rare, more often impotence and decreased libido (Nejm 1978;299:847); presentation is later, so have higher incidence of hypopituitarism and visual field losses (Ann IM 1986;105:238)

Si:Galactorrhea, ie, any amount of milky substance expressible, no correlation of amount with prolactin level or tumor size

Course ⬆ ⬇

Usually benign, esp the idiopathic or microadenoma types (Ann IM 1984;100:115), although skeletal and cardiovascular consequences of hypogonadism, if present, must be considered

Complications ⬆ ⬇

Panhypopituitarism

Visual field cuts w macroadenoma (>1 cm), esp during pregnancy, rare w microadenomas (Ann IM 1994;121:473)

Osteoporosis due to low estrogen/androgen levels reversible with rx (Nejm 1986;315:542)

ASHD from hypogonadism (estrogen lack)

Lab and Xray ⬆ ⬇

Lab:

Chem:Prolactin >100 ngm/cc is likely adenoma, returns to normal w rx; r/o medication causes of moderate elevations (usually <100 ngm/cc): metoclopramide (Reglan), phenothiazines, butyrophenomes, TCAs, risperidone, MAOIs, verapamil, reserpine, Aldomet

Path:Prolactin-staining microadenoma, but 27% of normals in autopsy series also have? (Nejm 1981;304:156)

Xray:Gadolinium-enhanced MRI (Nejm 1991;324:1555), but 10% false pos in general population (Ann IM 1994;120:817); CT, 15-20% false pos (D. Federman 3/85). Microadenoma = <10 mm diameter, macroadenoma = >10 mm

Treatment ⬆

Rx:

Pregnancy and nursing risks are small with idiopathic or microadenomas

Medical rx w dopamine agonists like:

  • Bromocriptine (Parlodel) 1.25-20 mg po qd divided, eg, 1.25-2.5 mg po hs with snack × 3-7 d, then 2.5 bid increased to tid gradually; try for higher doses until prolactin level is suppressed to decrease tumor size (Nejm 1985;313:656) in about 1/2; 1st choice if attempting pregnancy, stop as soon as pregnant; adverse effects: hypotension, cost, nausea, peptic ulcer disease, headache, dizziness, Raynaud's at high doses
  • Cabergoline (Dostinex) 0.25-1 mg po biw, better tolerated and twice as effective, 83% become normoprolactinemic vs 59% w bromocriptine (Nejm 1994;331:904); can try withdrawing after 3 yr (Nejm 2003;349:2023), 25% recurrence off med. But causes cardiac valve fibrosis and regurgitation (Nejm 2007;356:29,39)
  • Surgical transsphenoidal resection unreliable but can try if fail medical rx