Hyperprolactinemia

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If the pt is taking a medication that is known to cause hyperprolactinemia, the drug should be withdrawn, if possible. A pituitary MRI should be performed if the underlying cause of PRL elevation is unknown. Resection of hypothalamic or sellar mass lesions can reverse hyperprolactinemia due to stalk compression. Medical therapy with a dopamine agonist is indicated in microprolactinomas for control of symptomatic galactorrhea, for restoration of gonadal function, or when fertility is desired. Alternatively, estrogen replacement may be indicated if fertility is not desired, but tumor size should be carefully monitored. Dopamine agonist therapy for macroprolactinomas generally results in both adenoma shrinkage and reduction of PRL levels. Cabergoline (initial dose 0.5 mg a week, usual dose 0.5-1 mg twice a week) or bromocriptine (initial dose 0.625-1.25 mg qhs, usual dose 2.5 PO three times a day) are the two most frequently used dopamine agonists. Cabergoline is the more effective and better-tolerated drug. These medications should initially be taken at bedtime with food, followed by gradual dose increases, to reduce the side effects of nausea and postural hypotension. Other side effects include constipation, nasal stuffiness, dry mouth, nightmares, insomnia, or vertigo; decreasing the dose usually alleviates these symptoms. Dopamine agonists may also precipitate or worsen underlying psychiatric conditions. Cardiac echocardiography is prudent before starting cabergoline therapy as there has been concern about an association with valvular heart disease. In pts with microadenomas successfully treated (normal PRL, full tumors shrinkage), therapy may be withdrawn after 2 years, followed by careful monitoring for tumor recurrence. Spontaneous remission of microadenomas, presumably caused by infarction, occurs in some pts. Surgical debulking may be required for macroprolactinomas that do not adequately respond to medical therapy.

Women with microprolactinomas who become pregnant should discontinue dopaminergic therapy, as the risk for significant tumor growth during pregnancy is low. In those with macroprolactinomas, visual field testing should be performed at each trimester. A pituitary MRI should be performed if severe headache and/or visual defects occur.

Acromegaly

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The goal of treatment is to control GH and IGF-I hypersecretion, ablate or arrest tumor growth, ameliorate comorbidities, restore mortality rates to normal, and preserve pituitary function. The primary treatment modality for acromegaly is transsphenoidal surgery. GH levels are not normalized by surgery alone in many pts with macroadenomas; in those, somatostatin analogues provide adjunctive medical therapy that suppresses GH secretion with modest to no effect on tumor size. Octreotide (50 µg SC three times a day) is used for initial therapy to determine response. Once a positive response and tolerance of side effects (nausea, abdominal discomfort, diarrhea, flatulence) are established, pts are changed to long-acting depot formulations (octreotide LAR 20-30 mg IM every 2-4 weeks or lanreotide autogel 90-120 mg IM once a month). For those resistant to octreotide, pasireotide, with preferential SST5 binding, has been shown to exhibit efficacy. Dopamine agonists (bromocriptine, cabergoline) can be used as adjunctive therapy but are generally not very effective. The GH receptor antagonist pegvisomant (10-20 mg SC daily) can be added in pts who do not respond to somatostatin analogues. Pegvisomant is highly effective in lowering IGF-I levels but does not lower GH levels or decrease tumor size. Pituitary irradiation may also be required as adjuvant therapy but has a slow therapeutic onset and a high rate of late hypopituitarism.