Assessment of baseline pituitary function before Gamma Knife radiosurgery is mandatory to determine the need for any hormone replacement therapy. Because radiation therapy is expected to cause damage to the normal pituitary gland, patients should be evaluated at least every 6 mo for development of secondary hypothyroidism, secondary hypogonadism, secondary adrenal insufficiency, and GH deficiency. Radiation therapy does not usually cause diabetes insipidus (DI), but patients should be asked about excessive urination and thirst. Patients should be educated about the symptoms of hypothyroidism, adrenal insufficiency, and hypogonadism and instructed to return earlier should such symptoms develop.
Patients with acromegaly should be treated with a somatostatin analog (Sandostatin, Sandostatin LAR, Lanreotide) to reduce circulating GH- and insulin-like growth factor (IGF)-1 concentrations after treatment with the Gamma Knife. A report of a decrease in the efficacy of the Gamma Knife therapy in patients receiving a somatostatin analog at the time of radiosurgery compared with untreated patients resulted in the recommendation that medical therapy be given after Gamma Knife therapy (5,6). Although these findings have not been confirmed, it is reasonable to withhold medical treatment until at least 6 wk after radiosurgery because medical treatment may delay the effectiveness of Gamma Knife treatment. Similarly, patients with a prolactinoma may have less favorable results from Gamma Knife treatment if they are receiving a dopamine agonist at the time of radiosurgery (7). Although this observation has not been confirmed, it is prudent to delay adjunctive dopamine agonist therapy until 6 wk after Gamma Knife treatment if this observation is validated in studies of other patients. Patients with CD are treated with a drug to reduce adrenal cortisol production (e.g., ketoconazole, metopirone). Because these medications do not act on the pituitary gland and control of excessive cortisol production is important, these patients may be given medical therapy at the time of Gamma Knife treatment. Patients treated with ketoconazole must be followed closely for liver toxicity; regular measurement of liver enzymes is also indicated.
After Gamma Knife treatment patients are evaluated every 6 mo to determine if the therapy has reduced the excessive hormone level to normal and to identify new hormone deficiency or deficiencies. Because the patient with acromegaly or
CD will be taking medication to control hormone hypersecretion, the medication(s) should be discontinued for 1 mo before evaluation. In the case of patients with acromegaly receiving a long-acting somatostatin analog (Sandostatin LAR, Lanreotide), the suppressive effect may last longer than 1 mo. In this situation, if the serum IGF-1 level is normal, medication should be withheld and the serum IGF-1 level should be repeated 2 to 3 mo after stopping the medication. In patients with CD treated with ketoconazole to reduce adrenal cortisol secretion, a 24-h urine-free cortisol (UFC) should be measured 1 mo after discontinuation of the drug. Patients with a prolactinoma may have a partial response to a dopamine agonist drug (bromocriptine, norprolac, pergolide, cabergoline), and this medication should be administered if there is any evidence of a positive response. As with other medical therapies, the dopamine agonist should be discontinued every 6 mo for 4 to 6 wk, at which time a serum PRL is measured to evaluate the response to Gamma Knife treatment.
New hormone deficiency or deficiencies are identified by obtaining a thorough clinical history and physical examination and measurement of appropriate hormone concentrations. Fatigue, weight gain, decreased mental alertness, and constipation suggest hypothyroidism. Fatigue, orthostatic symptoms, diminished appetite, and weight loss suggest adrenal insufficiency. A decrease in libido or erectile dysfunction suggests hypogonadism in men and a change in menses (irregular menses, amenorrhea), diminished libido, or hot flashes suggest gonadal failure in women. The symptoms of GH deficiency overlap with other hormone deficiencies and include fatigue, decreased exercise tolerance, increase in abdominal adiposity, and diminished sense of well-being. Appropriate hormone studies include measurement of serum thyroxine (or free thyrox-ine, free T4), early morning cortisol, testosterone (men), and estradiol (women). Measurement of serum thyroid-stimulating hormone (TSH) is not helpful and may be misleading in a patient with secondary hypothyroidism. Assessment of GH production usually requires a stimulation test, because the serum IGF-1 (overall indicator of GH production) may be normal because IGF-1 production is influenced by nutrition and probably by other factors. The most rigorous test of GH secretion is the insulin-induced hypoglycemia test that also allows for assessment of adenocorticotropin hormone (ACTH)-cortisol reserve. Other acceptable stimulation tests for GH deficiency include iv arginine or arginine plus GH-releasing hormone (GHRH).
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