The treatment of choice for Cushing disease is transsphenoidal resection. The remission rate is approximately 70% to 90% and the recurrence rate is 5% to 10% at 5 years and 10% to 20% at 10 years in patients with microadenomas who undergo surgery by an experienced surgeon (160– 164). Patients with macroadenoma have lower remission rates (<60%) and higher recurrence rates (12% to 45%) (165–167). Following surgery, transient diabetes insipidus and enduring compromise of anterior pituitary secretion of growth hormone, gonadotropins, and TSH are common (167,168).
Fractionated external beam radiotherapy or stereotactic radiosurgery is used to treat patients with Cushing disease in whom transsphenoidal microsurgery was not successful or in patients who are poor surgical candidates. This therapy can achieve control of hypercortisolemia in approximately 50% to 60% of patients within 3 to 5 years (155,169,170). Hypopituitarism is the most common side effect of pituitary irradiation, and long-term follow-up is essential to detect relapse, which can occur after an initial response to radiotherapy.
High-voltage external pituitary radiation (4,200 to 4,500 cGy) is given at a rate not exceeding 200 cGy per day. Only 15% to 25% of adults show total improvement, but approximately 80% of children respond (168,171).
Mitotane can be used to induce medical adrenalectomy during or after pituitary radiation (157). The role of medical therapy is to prepare the severely ill patient for surgery and to maintain normal cortisol levels while a patient awaits the full effect of radiation. Occasionally, medical therapy is used for patients who respond to therapy with only partial remission. Adrenal enzyme inhibitors include aminoglutethimide, metyrapone, trilostane, and etomidate.
A combination of aminoglutethimide and metyrapone may cause a total adrenal enzyme block, requiring corticosteroid-replacement therapy. Ketoconazole, an FDA-approved antifungal agent, inhibits adrenal steroid biosynthesis at the side arm cleavage and 11β-hydroxylation steps. The dose of ketoconazole for adrenal suppression is 600 to 800 mg per day for 3 months to 1 year (172). Ketoconazole is effective for long-term control of hypercortisolism of either pituitary or adrenal origin.
Nelson syndrome results from adenomatous progression of ACTH-secreting cells in patients with Cushing syndrome treated by bilateral adrenalectomy. The macroadenoma that causes this syndrome produces sellar pressure symptoms of headaches, visual field disturbances, and ophthalmoplegia. Extremely high ACTH levels in Nelson syndrome are associated with severe hyper-pigmentation (melanocyte-stimulating hormone activity). The treatment is surgical removal or radiation. The offending adenomatous tissue is often resistant to complete surgical removal (173). This syndrome reportedly complicates 10% to 50% of bilateral adrenalectomy cases. Measuring pituitary MRI and ACTH plasma levels at regular intervals after bilateral adrenalectomy will allow detection of the early progression of corticotroph tumors and the possibility of cure by surgery, particularly with microadenomas (155). Nelson syndrome is less common today because bilateral adrenalectomy is less frequently used as initial treatment.
CAH is transmitted as an autosomal recessive disorder. Several adrenocortical enzymes necessary for cortisol biosynthesis may be affected. Failure to synthesize the fully functional enzyme has the following effects: 1.
A relative decrease in cortisol production.