Transsphenoidal microsurgical results of female patients with prolactinomas

Abstract

Objective

We investigated surgical cure rate and surgical complications of patients with macroprolactinomas who desired pregnancy to evaluate the efficacy of transsphenoidal surgery.

Methods

Surgical cure rate was investigated in 138 female patients who were under 40 years old.

Results

We found a significant correlation between serum prolactin levels and adenoma volume (r = 0.004; p < 0.0001), adenoma volume and age (r = −0.213; p < 0.03), and proliferative index of the adenoma and age (r = −0.15; p < 0.007). Seventy-seven out of 81 patients with enclosed macroadenoma were considered cured, and therefore the overall surgical cure rate was 95%. However, during long-term follow-up, recurrence of adenomas with hyperprolactinemia was seen in 5 out of 81 patients (6%), and the long-term cure rate in patients with enclosed macroadenomas was 89%. Adenomas that did not invade the cavernous sinus showed a significantly higher surgical curability and lower serum prolactin levels, and a smaller size than those adenomas that invaded the cavernous sinus.

Conclusions

The long-term surgical cure rate was found to be 89% and this success rate far surpasses the complication rate of 39% during pregnancy by dopamine agonist therapy. Thus, transsphenoidal surgery should be considered as a first-line treatment for female patients who desire pregnancy.

Introduction

Prolactinomas are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists (DAs) is highly effective in the majority of cases and represents the mainstay of therapy. As a result, transsphenoidal surgery for prolactinoma is indicated for a distinct number of indications such as non-responders to medical therapy, intolerance of DAs, and cerebrospinal fistula due to tumor invasion.

There is a significant negative correlation between age and the Ki-67 labeling index in female patients with prolactinoma [36]. Therefore, the younger their age, the higher the proliferative activity of the prolactinoma becomes. However, this negative correlation is not observed in male patients with prolactinomas [28]. The optimal management for patients with prolactinomas may vary according to sex, size of the adenoma, and age. In young female patients, changes in hormone secretion in accordance with pregnancy and delivery have a severe effect on proliferative activity of adenomas. The placental estrogen surge during pregnancy has been shown to induce the mitotic activity of lactotroph cells [19], [21]. Since prolactinoma cells express the estrogen receptor [18], it is reasonable that prolactinomas can greatly increase during pregnancy.

In pregnant women with microprolactinomas, the risk of symptomatic tumor enlargement is low [5], [14]. Therefore, most pregnant women with microadenomas can be managed safely during pregnancy. However, the risk of tumor enlargement in pregnancy is substantially greater for patients with macroprolactinomas [5], [14]. Therefore, specialist care and monitoring is generally required for women with macroprolactinomas during pregnancy [19]. Thirty-nine percent of pregnant women with macroprolactinomas have symptoms of tumor enlargement such as headaches or visual disturbance [6], [9], [13], [23], [26], [27], [33], [37]. For these reasons, it is preferable to have a preventive therapeutic option to avoid serious complications and special care and monitoring during pregnancy. The most preventive approach to avoid serious complications during pregnancy is to perform a prepregnancy transsphenoidal surgical debulking of the tumor.

In this study, we evaluated young female patients (under 40 years old) and evaluated the surgical results and complications of transsphenoidal (TS) surgery to determine if it is appropriate for first-line treatment of female prolactinomas.