We identified 54 patients with CD and excluded 2 patients for a previous glaucoma surgery. We included 52 patients (38.4 ± 12.4 years old) with CD, 43 patients with acromegaly, and another 44 patients with NFPA in this study. Clinical characteristics, radiological assessment, endocrine tests are listed in Table 1. The majority of patients with CD were female (78.8%), had hypertension (63.4%), and were with a microadenoma (92.3%). 24 h UFC elevated in all these patients with normal or elevated ACTH. Comparing to patients with acromegaly or NFPA, patients with CD were younger, more likely to be female, more likely to have hypertension or diabetes mellitus, and less likely to harbor a macroadenoma.
Table 1
Basic characteristics and ocular manifestation in patients with different type of pituitary adenomas
|
Patients with CD
(N = 52)
|
Patients with acromegaly
(N = 43)
|
Patients with NFPA
(N = 44)
|
Age (years old)
|
38.4 ± 12.4
|
47.3 ± 12.6
|
49.3 ± 13.7
|
Gender (Female)
|
41 (78.8%)
|
20 (46.6%)
|
21 (47.7)
|
Body mass index (kg/m2)
|
25.5 ± 4.3
|
25.5 ± 3.6
|
24.4 ± 3.4
|
Comorbidities
|
|
|
|
Diabetes Mellitus
|
19 (36.5%)
|
14 (32.6%)
|
8 (18.2%)
|
Hypertension
|
33 (63.4%)
|
14 (32.6%)
|
6 (13.6%)
|
Tumor characteristics
|
|
|
|
Macroadenoma
|
4 (7.7%)
|
34 (79.1%)
|
39 (88.6%)
|
Microadenoma
|
48 (92.3%)
|
9 (20.9%)
|
5 (11.4%)
|
Nonequivocal tumor
|
28/48 (58.3%)
|
NA
|
NA
|
Equivocal tumor
|
20/48 (41.7%)
|
NA
|
NA
|
CS invasiveness
|
2 (3.8%)
|
11 (25.6%)
|
12 (27.3%)
|
Endocrinological tests
|
|
|
|
ACTH (pg/ml)
|
65 [44–97]
|
NA
|
NA
|
24 h UFC (ULN)
|
3.3 [2.0–6.1]
|
NA
|
NA
|
GH (ng/ml)
|
NA
|
10.4 [4.8–22.8]
|
NA
|
IGF-1 (ULN)
|
NA
|
2.4 [1.7–3.1]
|
NA
|
Free T4 (pmol/l)
|
14.7 ± 2.9
|
19.2 ± 3.7
|
12.5 ± 3.2
|
Free T3 (pmol/l)
|
3.4 ± 0.8
|
4.8 ± 0.9
|
4.0 ± 0.6
|
Intraocular pressure (mmHg)
|
|
|
Left
|
19.4 ± 5.4
|
17.5 ± 2.3
|
17.8 ± 2.6
|
Right
|
20.0 ± 7.1
|
18.6 ± 7.0
|
17.4 ± 2.4
|
Ocular hypertension
|
|
|
|
Left
|
9 (17.3%)
|
3 (7.0%)
|
2 (4.5%)
|
Right
|
12 (23.1%)
|
1 (2.3%)
|
2 (4.5%)
|
Glaucomatous visual field
|
|
|
|
Left
|
3 (5.8%)
|
0 (0.0%)
|
0 (0.0%)
|
Right
|
4 (7.7%)
|
0 (0.0%)
|
0 (0.0%)
|
CD: Cushing’s Disease, NFPA: nonfunctioning pituitary adenoma, CS: cavernous sinus, ACTH: adrenocorticotropic hormone, UFC: urine free cortisol, GH: growth hormone, IGF-1: insulin growth factor-1, NA: not available |
Intraocular pressure was higher in patients with CD (left 19.4 ± 5.4 mmHg and right 20.0 ± 7.1 mmHg) than in patients with acromegaly (left 17.5 ± 2.3 mmHg and right 18.6 ± 7.0 mmHg, p = 0.033) and patients NFPA (left 17.8 ± 2.6 mmHg and right 17.4 ± 2.4 mmHg, p = 0.005). Twenty-one eyes (20.2%) in patients with CD were diagnosed with ocular hypertension comparing to four eyes (4.7%) in the acromegaly group and four eyes (4.5%) in the NFPA group. Thus, the odds ratio of developing ocular hypertension in patients with CD was 5.1 (95% CI, 1.3–25.1, p = 0.029) and 6.6 (95% CI, 1.8–30.3, p = 0.007), compared with patients with acromegaly and patients with NFPA, respectively. Seven eyes (four patients, 6.7%) with ocular hypertension had glaucomatous visual field damage in patients with CD, but none of the eyes in the acromegaly group or the NFPA group.
We also compared the thickness of p-RNFL in patients with CD and patients with acromegaly but did not observe statistical difference between the two groups (average RNFL, 109.6 µm in CD and 113.0 µm in acromegaly, p = 0.153; superior RNFL, 132.2 µm in CD and 138.6 µm in acromegaly, p = 0.099, inferior RNFL, 142.7 µm in CD and 146.5 µm in acromegaly, p = 0.288)
Figure 1 illustrated a typical patient with CD who was diagnosed with IOP. A 40 years old female with central obesity and skin striae was admitted to our center. She was diagnosed with hypertension and osteoporosis five years ago. Pre-operation evaluations confirmed pituitary-originated hypercortisolemia with increased 24 h UFC higher than three folds of the normal upper limit. Preoperative MRI and intraoperative findings confirmed a tumor located on the left side of the pituitary. The patient had increased IOP to 25 mmHg on the left eye, and the visual field demonstrated nasal scotoma. P-RNFL was within the normal range. IOP on the right eye increased to 50 mmHg and was suspected blind due to glaucoma.
We further investigated the risk factors for developing ocular hypertension in patients with CD. We regressed the outcome (patients developing ocular hypertension) on possible risk factors (age, gender, BMI, comorbidities, tumor characteristics, endocrine tests) and found that only 24 h UFC was associated with ocular hypertension (p = 0.025). Patients with 24 h UFC higher than three folds of the normal upper limit were more likely to develop ocular hypertension than patients who had lower 24 h UFC (OR 19.4, 95% CI 1.7–72.6).
The majority of the patients with CD had remission (49/52, 94.3%) after surgical treatment. We further reviewed postoperative IOP change in patients with functional pituitary adenomas (Fig. 2). IOP decreased to 16.9 ± 4.3 mmHg in the left eye and 16.9 ± 4.8 mmHg in the right eye at one-month follow-up in patients with CD. Afterward, the IOP kept constant at three-month follow-up (16.6 ± 3.1 mmHg in the left eye and 17.4 ± 2.9 mmHg in the right eye). While patients with acromegaly had constant IOP (left 16.5 ± 2.4 mmHg and right 16.6 ± 2.2 mmHg at one-month, left 16.8 ± 2.3 mmHg and right 16.8 ± 2.2 mmHg at three-month) throughout the presurgical and follow-up period. Among the 7 eyes with glaucomatous visual field damage, 6 eyes improved on the follow up visual field testing with one eye similar.