Radiation dose to neuroanatomical structures of pituitary adenomas and the effect of Gamma Knife radiosurgery on pituitary function

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OBJECTIVE

Gamma Knife radiosurgery (GKRS) provides a safe and effective management option for patients with all types of pituitary adenomas. The long-term adverse effects of targeted radiation to the hypothalamic-pituitary axis in relationship to radiation dose remain unclear. In this retrospective review, the authors investigated the role of differential radiation doses in predicting long-term clinical outcomes and pituitary function after GKRS for pituitary adenomas.

METHODS

A cohort of 236 patients with pituitary tumors (41.5% nonfunctioning, 58.5% functioning adenomas) was treated with GKRS between 1998 and 2015. Point dosimetric measurements, with no minimum volume, to 14 consistent points along the hypothalamus bilaterally, pituitary stalk, and normal pituitary were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiological, and endocrine outcomes.

RESULTS

With a median follow-up duration of 42.9 months, 18.6% of patients developed new loss of pituitary function. The median time to endocrinopathy was 21 months (range 2–157 months). The median dose was 2.1 Gy to the hypothalamus, 9.1 Gy to the pituitary stalk, and 15.3 Gy to the normal pituitary. Increasing age (p = 0.015, HR 0.98) and ratio of maximum dose to the pituitary stalk over the normal pituitary gland (p = 0.013, HR 0.22) were independent predictors of new or worsening hypopituitarism in the multivariate analysis. Sex, margin dose, treatment volume, nonfunctioning adenoma status, or ratio between doses to the pituitary stalk and hypothalamus were not significant predictors.

CONCLUSIONS

GKRS offers a low rate of delayed pituitary insufficiency for pituitary adenomas. Doses to the hypothalamus are low and generally do not portend endocrine deficits. Patients who are treated with a high dose to the pituitary stalk relative to the normal gland are at higher risk of post-GKRS endocrinopathy. Point dosimetry to specific neuroanatomical structures revealed that a ratio of stalk-to-gland radiation dose of 0.8 or more significantly increased the risk of endocrinopathy following GKRS. Improvement in the gradient index toward the stalk and normal gland may help preserve endocrine function.

ABBREVIATIONS ACTH = adrenocorticotropic hormone; GH = growth hormone; GKRS = Gamma Knife radiosurgery; HP = hypothalamic-pituitary; IGF-1 = insulin-like growth factor–1; SRS = stereotactic radiosurgery; TSH = thyroid-stimulating hormone.

Article Information

Correspondence Jason P. Sheehan: University of Virginia, Charlottesville, VA. jsheehan@virginia.edu.

INCLUDE WHEN CITING Published online April 12, 2019; DOI: 10.3171/2019.1.JNS182296.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

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    Studies of a 54-year-old man who originally presented with progressive decline of vision. Biochemical findings were consistent with the diagnosis of a nonfunctioning adenoma. The patient underwent pure endoscopic endonasal transsphenoidal resection. Following surgery, his vision problems improved, except for subtle deficits of the lower quadrant of the visual field. Serial imaging of the brain demonstrated substantial decompression of the optic chiasm, with a small residual tumor of the cavernous sinus on the right side. The patient then underwent GKRS 15 months after resection. All images are coronal sections of T1-weighted MR images with gadolinium contrast and fat suppression. A: Image obtained prior to resection showing a 2.5 × 2.1 × 2.6–cm sellar suprasellar homogeneously enhancing lesion with mass effect on the optic chiasm. B: Image obtained prior to GKRS. Note the enhancing soft tissue centered within the right cavernous sinus, measuring approximately 8 × 9 × 10 mm. C: Image obtained at the last follow-up demonstrating a decrease in the right cavernous sinus tissue compared with pretreatment examination. I = inferior; R = right.

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    This is the same treatment scan acquired at the time of GKRS for the 54-year-old man featured in Fig. 1B. Point dosimetry showing where treatment measures were obtained along the hypothalamus, pituitary stalk, and pituitary gland. Fourteen distinct points along the HP axis were selected: 3 along both the left and right hypothalamus, 3 to the pituitary gland, and 5 to the pituitary stalk. LH = left hypothalamus; NP = normal pituitary; PS = pituitary stalk; RH = right hypothalamus. Figure is available in color online only.

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    Cumulative endocrinopathy rate based on timing after GKRS. Using a multivariate analysis, there was a significant difference in the rate of endocrinopathy based on the ratio of maximum dose to the pituitary stalk over the normal pituitary gland, with a threshold of 0.8. Overall, 18.6% of patients developed endocrinopathy in a median of 21 months (range 2–157 months). Figure is available in color online only.

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