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HYPERPROLACTINEMIA
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ESSENTIALS OF DIAGNOSIS
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Women: Menstrual cycle disturbances (oligomenorrhea, amenorrhea); galactorrhea; infertility Men: Hypogonadism; decreased libido and erectile dysfunction; infertility Elevated serum PRL CT scan or MRI often demonstrates pituitary adenoma
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Prognosis
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Patients with acromegaly have increased morbidity and mortality from cardiovascular disorders and progressive acromegalic symptoms; those who are treated and have a glucose-suppressed serum GH level less than 25 ng/mL (radioimmunoassay) or under 1 ng/mL (immunofluorometric assay) and normal age-adjusted serum IGF-I levels have reduced morbidity and mortality Transsphenoidal pituitary surgery is successful in 80 90% of patients with tumors less than 2 cm in diameter and GH levels less than 50 ng/mL Extrasellar extension of the pituitary tumor, particularly cavernous sinus invasion, reduces the likelihood of surgical cure Adjuvant medical therapy has been quite successful in treating patients who are not cured by pituitary surgery Postoperatively, normal pituitary function is usually preserved Soft tissue swelling regresses but bone enlargement is permanent Hypertension frequently persists despite successful surgery Conventional radiation therapy (alone) produces a remission in about 40% of patients by 2 years and 75% of patients by 5 years after treatment Gamma knife or cyberknife radiosurgery reduces GH levels an average of 77%, with 20% of patients having a full remission after 12 months Patients with pituitary adenomas that abut the optic chiasm can be treated with cyberknife radiosurgery, controlling tumor growth and preserving vision in most patients Heavy particle pituitary radiation produces a remission in about 70% of patients by 2 years and 80% of patients by 5 years Radiation therapy eventually produces some degree of hypopituitarism in most patients Conventional radiation therapy may cause some degree of organic brain syndrome and predisposes to small strokes Patients must receive lifelong follow-up, with regular monitoring of serum GH and IGF-I levels Serum GH levels over 5 ng/mL and rising IGF-I levels usually indicate a recurrent tumor Hypopituitarism may occur, due to the tumor itself, pituitary surgery, or radiation therapy Hypopituitarism may develop years following radiation therapy, so patients must have regular clinical monitoring of their pituitary function
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Elevated serum PRL can be caused by numerous conditions (Table 26 2) PRL-secreting pituitary tumors are more common in women than in men and are usually sporadic but may rarely be familial as part of MEN 1 Most are microadenomas (< 1 cm in diameter) that do not grow even with pregnancy or oral contraceptives However, some giant prolactinomas can spread into the cavernous sinuses and suprasellar areas; rarely, they may erode the floor of the sella to invade the sinuses
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Clinical Findings
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A Symptoms and Signs
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Hyperprolactinemia may result in hypogonadotropic hypogonadism and reduced fertility Men usually have erectile dysfunction and diminished libido; gynecomastia sometimes occurs but rarely with galactorrhea Women may note oligomenorrhea or amenorrhea, although some women continue to menstruate normally Galactorrhea, defined as lactation in the absence of nursing, is common Of women with secondary amenorrhea and galactorrhea, about 70% have hyperprolactinemia Untreated hypogonadism ultimately increases the risk of developing osteoporosis Pituitary prolactinomas may cosecrete GH and cause acromegaly (see above) Large tumors may cause headaches, visual symptoms, and pituitary insufficiency
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B Laboratory Findings
Evaluate for conditions known to cause hyperprolactinemia, particularly pregnancy (serum hCG), hypothyroidism (serum
CMDT 2008
FT4 and TSH), renal failure (BUN and serum creatinine), cirrhosis (clinical evaluation and serum bilirubin and liver enzymes) and hyperparathyroidism (serum calcium) Men are evaluated for hypogonadism with determinations of serum total and free testosterone, LH, and FSH Women who have amenorrhea are assessed for hypogonadism with determinations of serum estradiol, LH, and FSH An assay for macroprolactinemia should be considered for patients with hyperprolactinemia who are relatively asymptomatic and have no apparent cause for hyperprolactinemia Patients with pituitary macroadenomas (> 3 cm in diameter) should have PRL measured on serial dilutions of serum, since IRMA assays may otherwise report falsely low titers, the high-dose hook effect Patients with macroprolactinomas or manifestations of possible hypopituitarism should be evaluated for hypopituitarism as described above
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