ACTH secreting – delayed postoperative radiosurgery of gland for recurrent pathology-negative cushing disease

Skull Base Region	Sella turcica
Histopathology	Cushing disease
Prior Surgical Resection	Yes
Pertinent Laboratory Findings	Initial 24-hour urinary free cortisol: 142 mcg Final follow-up 24-hour urinary-free cortisol: 18 mcg

Case description

A 36-year-old woman with new-onset vision changes was diagnosed with central serous retinopathy by her ophthalmologist and treated with laser therapy. When her symptoms returned, she sought a second opinion, which prompted measurements of the pituitary hormones. Her 24-hour urinary-free cortisol levels were elevated up to 142 mcg/24 h. Two 1-mg dexamethasone suppression tests failed to suppress her serum cortisol, although an 8-gram overnight dexamethasone suppression test did result in appropriate cortisol suppression. Inferior petrosal sinus sampling confirmed a pituitary etiology and a 3T MRI revealed a 6 mm × 5 mm adenoma in the right anterior pituitary gland ( Figure 3.13.1 ).

At that time, she was complaining of fatigue, anxiety, easy bruising, and hair thinning, in addition to vision changes. The decision was made to pursue transsphenoidal resection. During surgery, no discrete tumor was visualized, but two suspicious areas were removed, leaving between 30% and 40% of the anterior lobe behind. Surgical pathology showed no definite adenoma but identified Crooke hyaline changes, indicating excess adrenocorticotropic hormone (ACTH) secretion. Her symptoms resolved by postoperative day 4, and morning cortisol and ACTH levels dropped to within normal limits at 1.9 mcg/dL and <5 pg/mL, respectively. Thus, she was diagnosed with pathology-negative Cushing disease (CD).

The patient remained symptom-free for 2 years postoperatively, but then noticed a recurrence of vision deficits as well as fatigue, easy bruising, anxiety, and difficulty sleeping. An endocrine workup showed elevated 24-hour urinary-free cortisol to 92 mcg/24 h. MRI showed no evidence of focal mass ( Figure 3.13.2 ). Therefore, the decision was made to pursue Gamma Knife Radiosurgery (GKRS) treatment for the remaining gland ( Figure 3.13.3 ).

Radiosurgery Machine	Gamma knife
Radiosurgery Dose (Gy)	24, at 50% isodose line
Number of Fractions	1

Critical Structure	Dose Tolerance
Optic nerve/chiasm	10 Gy maximum point dose <0.2 cc >8 Gy
Brainstem	15 Gy maximum point dose <1 cc >10 Gy
Cranial nerves in cavernous sinus	Not fully defined but significantly more resistant than the anterior optic apparatus Can be more sensitive if SRS follows another type of radiation therapy
Cavernous carotid artery	Very tolerant Rare cases of asymptomatic carotid stenosis after SRS for pituitary adenomas have been reported
Normal pituitary gland and pituitary stalk	Recommend limiting radiation exposure to the identifiable gland to <11.0 Gy and avoid whole-sella SRS whenever possible