Hypersecretion of adrenocorticotropic hormone (ACTH) is responsible for 80 % of endogenous Cushing’s syndrome, and pituitary adenomas are often the source of the hormone overproduction [27]. Microsurgical and endoscopic resection are the primary treatments for Cushing’s disease, but a surgical cure remains a challenge when there is tumor invasion of surrounding structures or difficult tumor delineation on imaging. Radiosurgery serves as an invaluable adjunctive treatment following resection in these circumstances. Although the updated 2008 guidelines from the Endocrine Society recommend the use of postoperative morning serum cortisol levels in establishing biochemical remission [27], there remains significant variability in the literature regarding its definition. Most studies define endocrine remission using normal serum cortisol or normal 24-h urinary-free cortisol (UFC). In a large study of 90 patients at the University of Virginia who were treated with GKRS, we have observed a biochemical remission rate of 54.4 % defined by 24-h UFC and a tumor control rate of 95.5 % [28, 29]. Table 7.2 shows a summary of radiosurgical results for Cushing’s disease from recent studies. These studies demonstrate a mean tumor control rate of 93 % (range, 77–100 %) and a biochemical remission rate of 54 % (range, 16.7–100 %), with a mean margin dose of 23.5 Gy (range, 15–35 Gy) [13, 22, 25, 26, 28–46].

In most series, rates of new neurologic deficits following radiosurgery are low, with an average of 2.8 % (range, 0–15.4 %), but the incidence of new endocrine deficit is higher, at a mean of 23 % (range, 0–68.8 %). These complication rates are both higher than what has been observed in radiosurgery for NFA; this difference could represent radiation damage to the normal pituitary and nerves secondary to the higher margin doses delivered to ACTH-secreting adenomas. Despite biochemical remission and hormone reduction offered by radiosurgery, late recurrence rates of up to 20 % have been reported, so long-term follow-up is very important for these patients [28, 40].

Adrenalectomy is the ultimate treatment for patients with Cushing’s disease refractory to conventional surgical, radiosurgical, and medical managements. Although definitive treatment for hypercortisolemia can be offered by adrenalectomy, up to 23 % of patients subsequently develop Nelson’s syndrome, which can lead to rapid growth of the adenoma and parasellar invasion [47]. Relatively few studies in the literature have evaluated the role of radiosurgery in the treatment of Nelson’s syndrome. In the largest series thus far, Mauermann et al. [48] observed a 90.9 % rate of tumor control and a 20 % rate of ACTH normalization in a population of 23 patients treated with GKRS. In a recent study of 22 patients treated with GKRS, Sheehan et al. [29] found the same hormone normalization rate of 20 %. Table 7.3 shows a summary of radiosurgical results for Nelson’s syndrome from recent studies. These studies show an average tumor control rate of 95 % (range, 82–100 %) and a hormone normalization rate of 30 % (range, 0–100 %), using a mean margin dose of 22 Gy (range, 12–28.7 Gy) [17, 32, 41, 48–51]. Despite the low hormone normalization rates reported in the series, studies have demonstrated significant reduction in ACTH following radiosurgery [48, 50, 51].

Common adverse effects of radiosurgery for Nelson’s syndrome include visual and hormonal deficits; recent series show the incidence of neurologic deficits to be 2.7 % (range, 0–9.1 %) and the incidence of hormonal deficits to be 32.6 % (range, 0–50 %). Current literature demonstrates that radiosurgery is effective in controlling tumor progression and reducing ACTH levels, but hormone normalization may be difficult to achieve with radiosurgery alone.

Although surgical resection remains the first-line treatment in most cases of acromegaly, endocrine cure by surgery alone is unlikely, particularly for patients with tumor involvement of the dura and cavernous sinus [52]. Because complete surgical resection may not always be feasible, radiosurgery provides a viable alternative or adjunct treatment for those who cannot tolerate first-line management or who have residual disease following surgery. Radiosurgery following surgical resections achieves almost total tumor control; in contrast, the average biochemical remission rate is only 48 % (range, 17–100 %) across recent series, using a mean margin dose of 23 Gy (range, 15–35 Gy) [13, 17, 22, 23, 25, 26, 29, 33, 35, 39, 40, 42, 43, 45, 53–70]. Precise criteria for biochemical remission following radiosurgery vary across case series. The most recent 2010 guidelines for remission have not been extensively validated following treatment with radiosurgery [71], and most studies define remission using a random serum growth hormone (GH) level less than 2 ng/mL, a GH level less than 1 ng/mL following an oral glucose tolerance test, or normal insulin-like growth factor-1 level adjusted for age and sex [72, 73]. In the largest study thus far, Sheehan et al. [29] reported a biochemical remission rate of 53 % in 130 patients treated with GKRS. More recently, in a smaller cohort of patients treated with GKRS, Franzin et al. [74] observed a more favorable remission rate of 60.7 %. Table 7.4 shows a summary of recent radiosurgical results for acromegaly.