張雲筑¹ 、李政家^2,3 、顏玉樹^2,3 、林登龍^1,3,4 、陳光國^1,3,4 、黃志賢^1,3,4

                                 ¹臺北榮民總醫院 泌尿部,²臺北榮民總醫院 神經醫學中心神經外科;

³國立陽明大學 醫學院 泌尿學科 ; ⁴書田泌尿科學研究中心

Yun-Chu Chang ¹, Cheng-Chia Lee^2,3, Yu-Shu Yen^2,3,

Alex T.L. Lin^1,3,4, Kuang-Kuo Chen^1,3,4, William J. Huang^1,3,4

¹ Department of Urology, ²Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital; ³ School of Medicine, ⁴Shu-Tien Urological Research Center, National Yang-Ming University, Taipei, Taiwan

 

Hypogonadism is common in men with pituitary tumors. Endoscopic trans-sphenoidal surgery (ETSS) and Stereotactic radiosurgery (SRS) including gamma-knife surgery (GKS) are the mainstay of treatment nowadays. However, the effects of these surgical treatments on the serum testosterone levels are not clear.

 

We retrospectively review the case log of male patients with pituitary tumors that were treated with ETSS and SRS in our institute from 2003 to 2015. Patients’ demographic data, tumor characteristics, and the hormone profiles before and after treatment (before and 3 days and 3 months after ETTS, and 1, 3, 5 years after adjuvant SRS) were collected for analysis. Hypogonadism was defined as blood levels less than 3.5 ng/mL in patients ≤ 40 years old or less than 2.8 ng/mL in patients > 40. Considering the strong correlation between hyperprolactinemia and hypogonadism, patients who had pure prolactinoma were excluded from this analysis. Statistics of the means were performed using the unpaired Student t-test, two-tailed McNemar test and Levene test while Wilcoxon sign rank test with Bonferroni correct method and Mann-Whitney U test were applied for post hoc multiple comparison.

 

Totally 50 patients were enrolled. The mean age at primary ETSS was 47.3 ± 17.2 years and mean BMI was 25.2 ± 3.0 kg/m² (Table 1). Patients all presented with a pituitary macroadenoma (mean size 31.5 ± 11.6 mm) on the pre-operative magnetic resonance imaging. Functional tumors accounts for 22%, including acromegaly in 18% and Cushing disease in 4%. Gonadotroph adenoma (58%) was the most common pathological finding, it was followed by plurihormonal adenoma (16%) and mammosomatotroph adenoma (14%). Apoplexy was noted in 10% of patients. Average SRS margin dose was 13.6 ± 1.5 Gy. Preoperative mean testosterone levels were 2.36 ± 1.96 ng/mL and the prevalence of hypogonadism was 68%. In all patients, drop of testosterone (mean= 1.61 ± 1.60 ng/mL) was noted 3 days after ETSS (P< 0.05). Three months after ETSS, the testosterone levels resumed gradually to the preoperative status (mean = 2.04 ± 1.77 ng/mL, P= 0.28). The average interval between ETSS and the consecutive adjuvant SRS was 20.1 ± 10.8 months. The incidence of hypogonadism before surgical treatment (68%) was similar to that after the ETSS (74% on the post-op 3rd days and 72% on the post-op 3 months) (Table 2). But the incidence of hypogonadism was much higher on the post-ETSS 3rd days than that at 1 year post-SRS (74% vs. 60%, P= 0.039), with 20% patients showed improvement of testosterone levels even after SRS. The serial follow-up testosterone levels showed no improvement on the post-SRS 1,3, and 5 years (2.44, 2.49, and 2.42, P = 0.88) and the prevalence of hypogonadism remained the same (60%, 44%, 54%, P= 0.61). In patient’s demographic data and other hormone profiles, the pre-op luteinizing hormone (LH, mean 3.53 ± 2.92 IU/L) levels correlated with the levels of testosterone at each follow-up. Regarding tumor characteristics, there was no strong relationship between the incidence of hypogonadism and the tumor pathology, the margin dose of SRS, the presence or the absence of apoplexy or the nature of function of the mass.

 

Hypogonadism is prevalent in patients with pituitary gland tumors before the surgical intervention. After ETSS, the testosterone levels dropped rapidly but resumed to the baseline 3 months later. The incidence of hypogonadism remained the same from pre-operative evaluation till 5 years post-SRS. The pre-ETSS LH levels could be a useful predictor for occurrence of hypogonadism after surgical intervention at short or intermediate term of follow-up. Testosterone replacement therapy could be discussed early after the operation especially in patients with initial hypogonadism.