Abstract
Objective: To explore the surgical therapeutic effects in the endocrine and reproductive system of women with prolactinoma at child-bearing age, and to investigate the potential influencing factors for therapeutic outcome. Methods: This retrospective study was performed using the medical records of 99 cases of female patients with pituitary PRL adenomas at child-bearing age, who underwent transsphenoidal surgery and took standard perioperative care from January, 2013 to June, 2013 in Huashan hospital, in which micro adenoma (≤1 cm) of 68 cases, large adenomas (> 1 cm) of 31 cases, 88 cases were total resection, 9 cases were subtotal resection, and 2 cases were massive resection. Retrospective study on the preoperative serum level of PRL, menstruation, galactorrhea and reproductive function, etc. Patients were followed up in 1, 3, 6 and 12 months after operation for endocrine indicators, the situation of menstruation and pregnancy. Results: Overall, 88.9%, 9.1%, and 2% patients underwent total, subtotal, and massive resection of prolactinoma in 99 cases of patients. Before accepting transsphenoidal surgery and standard care, all 99 cases with serum PRL level higher than normal 25 ng/ml, 71.7% (71 cases, all total resection) patients had their serum PRL < 25 ng/ml on the first day after surgery, and micro adenomas remission rate of 80.9% (55 cases) was significantly higher than 51.6% of large adenomas (16 cases) (P < 0.05); the postoperative PRL of 11 cases of total or massive resection in patients were not back to normal, Chi-square test results showed that the PRL remission rate after total resection were significantly higher than that of subtotal or massive resection (P < 0.01). 67.3% (66/98) irregular menstruation patients had menstruation recovery after surgery, in addition, total resection of the tumor, micro- adenoma, preoperative PRL < 200 ng/ml and first day of postoperative PRL ≤25 ng/ml were favorable factors for menstrual improvement (P < 0.05). 83.6% (51/61) of patients with galactorrhea symptoms got alliviated after surgery, but had no association to the types of tumor (P > 0.05). 14 patients out of 17 infertility patients got pregnant after surgery. Conclusion: Transsphenoidal operation combining standardized nursing measures is an effective way to treat pituitary PRL adenoma, and it has high cure rate on abnormal menstruation caused by pituitary PRL adenoma which can recover the fertility of female patients. The preoperative serum level of prolactin could be used as an indicator for postoperative improvement in the endocrine system. The serum level of prolactin on the first day after operation could accurately reflect prognosis, so be regarded as one of the assessment factors for surgical therapeutic effect.
Keywords: Woman, prolactinoma, endocrine, menstruation
Introduction
Pituitary adenoma is one of the common benign tumors in the Department of Neurosurgery, and prolactinoma is the most common subtype, accounting for 45% in functional pituitary tumors [1,2]. Pituitary prolactinoma occurs most often in young women (with clinical manifestations of amenorrhea, galactorrhea, infertility); it is a common cause of dysfunction of endocrine and reproductive systems [3]. PRL is a polypeptide hormone secreted by the anterior pituitary, the main function of PRL is to induce and maintain lactation. The small amount of PRL can be allowed for the synthesis of ovarian estrogen and progesterone, but a large amount of PRL may inhibit the synthesis of estrogen and progesterone. Over secretion of PRL by pituitary PRL adenoma causes ovulation disorders and brings great distress to the family and life of female patients. Therefore, it is the most concerned problem for the patients to choose the best possible way to recover the reproductive function.
The full name of transsphenoidal surgery is the transsphenoidal approach surgery, which has advantages of completely removing the tumor, simple approach in operation, faster recovery and fewer complications etc. With the constant improvement in neural navigation technology and neuro-endoscopy technology [4], transsphenoidal surgery shows a more significant effect in the treatment of pituitary adenomas, and it has become the primary option in treating pituitary PRL adenoma, especially preferred in treating micro-adenomas [5,6]. Scientific observation and nursing to bring an early recovery is an important part of increasing the cure rate of transsphenodal surgery [7].
In this paper, we reviewed the clinical data of 99 cases of female patients of pituitary PRL adenoma in Huashan hospital, such as preoperative symptoms, duration of disease, tumor size, serum PRL level, surgical resection, pathological section report and so on, and followed up postoperative endocrine index, menstrual improvement, pregnancy, etc. to explore the effect of transphenoidal surgery on improving women’s fertility function and its related factors in treating pituitary PRL adenoma.
Materials and methods
Case materials
A total of 99 female patients with prolactinoma at child-bearing age underwent transsphenoidal surgery in the Huashan Hospital (Shanghai, China) between January, 2013 and June, 2013. The age of patients ranged from 14 to 36 years old, median age was 25 years old; menstrual disorders time lasted from 3 months ~10 years, the median time was 18 months. All cases of the tumor specimens confirmed by immunehistochemical staining (IHC) were the pituitary PRL adenoma. Tumor, according to diameters, were divided into 3 class: micro-adenoma (diameter ≤1 cm), macro adenoma (diameter > 1 cm) and giant adenomas (diameter > 4 cm). This study included only 1 case of giant adenoma (diameter = 5.5 cm), which was classified into the macro adenoma group. The main clinical manifestations of patients were irregular menstruation, galactorrhea, infertility etc. The diagnosis and treatment of patients were shown in Table 1. The age range of child-bearing period is 16~36 years old.
Table 1.
Diagnosis and treatment of patients
| Diagnosis and treatment | Cases (n (%)) |
|---|---|
| Symptom | |
| Irregular menstruation | 98 (98.9%) |
| Menstrual cycle disorders | 25 (25.3%) |
| Primary amenorrhea | 7 (7.1%) |
| Secondary amenorrhea | 66 (66.7%) |
| Galactorrhea | 61 (61.6%) |
| Amenorrhea with galactorrhea | 44 (44.4%) |
| Tumor size | |
| Microadenoma (≤1 cm) | 68 (68.7%) |
| Total resection | 65 (65.7%) |
| Subtotal resection | 3 (3.0%) |
| Massive resection | 0 (0.00%) |
| Macroadenoma (> 1 cm) | 31 (31.3%) |
| Total resection | 23 (23.2%) |
| Subtotal resection | 6 (6.1%) |
| Massive resection | 2 (2.0%) |
| Invasive condition | |
| Invasive | 12 (12.1%) |
| Non invasiveness | 87 (87.9%) |
Inclusion criteria: (1) with irregular menstruation and other symptoms; (2) the serum level of PRL > 25 ng/ml; (3) tumor specimens were confirmed as PRL pituitary adenomas by immunohistochemistry; (4) patients treated with drug therapy failed or refused medical treatment. Exclusion criteria: (1) had a hysterectomy or double annex resection; (2) did not want to accept the full follow-up.
Research methods
Clinical examination
All patients were drew blood with empty stomach to check the endocrine indicators in the morning regularly when they were admitted to hospital, and obtain the blood by the same way for preoperative PRL detection in the second day. 99 patients, according to the serum level of PRL, were divided into 5 groups: > 200 ng/ml, 60~100 ng/ml, 100~200 ng/ml, 25~60 ng/ml, and < 25 ng/ml. Patients were drew blood with empty stomach in the morning of the first postoperative day to review all kinds of endocrine indicators and assess the effect of surgery.
Surgery method
Patient was supine on the tabel after general anesthesia, Head back 100-150 for nasal cavity disinfection, use a dilator to expand nasal cavity and a bone biting forceps to move nasal septum to fully expose the anterior and posterior wall of sphenoid sinus, use an osteotometo chisel the anterior wall of the sphenoidal sinusand micro rongeur to move the partial anterior wall of the sphenoidal sinus, use bipolar coagulation to hemostasis. Open the sellaturcica basement, confirm the dura and cross cut, with a scraping ring to remove tumor in block and then sent to inspection [8]. After total removal of the tumors, the saddle was collapsed, give a complete hemostasis and repair the sellaturcica basement, pack the nasal cavity with gauze. The patient with no symptom alleviation after resection should be treated with gamma knife sequentially [9].
Postoperative observation points: observe vital signs, pupil, consciousness, vision, view, urine color, urine quality, urine quantity, urine specific gravity and urine penetration pressure, as well as water electrolyte and acid-base imbalance, epilepsy and complications like cerebrospinal fluid rhinorrhea.
Nursing method
Perioperative period nursing included preoperative nursing, postoperative nursing and hospital discharge guidance [10]. Preoperative nursing is explaining relevant knowledge of pituitary adenoma to patients, eliminating the tension and fear to get their coordination. In addition, it also included preoperative examination and preoperative preparation, such as orally taking prednisone tablets, taking 0.5% chloramphenicol nose drops, picking off vibrissae etc. on the day before surgery. Postoperative care, in addition to the routine nursing after general anesthesia, also included removal of oral secretions to maintain airway patency. Patients who did not wake up after anesthesia should take lateral decubitus or supine, deflect head to a side, elevate head 150-300 after wake up; closely observed vital signs, consciousness, changes of pupil. After woke up, preliminary observed patient’s eye movements and vision and compared with postoperation; closely observed the urine volume and prevented a lack of posterior pituitary lobe; observed cerebrospinal fluid rhinorrhea and took timely measures; monitored and nursed pituitary function, such as keep warm, avoid infection and mental stimulation, monitor pituitary hormones in time and use hormone replacement therapy in severe condition according to doctor’s advice. Discharge guidance is giving patients living guidance beforedischarge, such as not forcing to blow your nose and cough, maintaining defecate unobstructed, preventing colds etc.
Postoperative follow-up
Patients were followed up for 1, 3, 6 and 12 months after operation. We followed up patients on the phone if they couldn’t take regular clinical review for special reasons. The postoperative re-examination mainly included: endocrine examination, enhanced images of magnetic resonance imaging (MRI) on the sellar region, and the status of menstruation and pregnancy.
Statistical methods
SPSS 16.0 software was used in experiment data processing, frequence and rate was used in statistical description, enumeration data was compared by χ2, and P < 0.05 or P < 0.01 was considered statistical significant.
Results and analysis
Transsphenoidal surgery significantly decreased serum PRL levels
Before accepting transsphenoidal surgery and the implementation of standard care, serum PRL level of all the 99 patients were higher than normal 25 ng/ml; after the first day of operation, 71.7% (71 cases) with serum PRL < 25 ng/ml which was within the normal rangeand they are all total tumor resection patients, among them, 80.9% (55 cases) pituitary adenoma patients had their PRL levels < 25 ng/ml on the first day after surgery patients, 51.6% (16 cases) macroadenoma patients had their PRL levels < 25 ng/ml on the first day after operation, the difference was significant (P < 0.05) (Table 2). However, the postoperative PRL level of the 11 cases who underwent subtotal or massive resection did not return to normal Chi-square test results showed that the PRLremission rate after total resection was significantly higher than those of subtotal or massive resection (P < 0.01).
Table 2.
Effect of transsphenoidal surgery on serum PRL level of pituitary PRL adenoma patients at first postoperative day
| PRL Level (ng/ml) | Pre-operation | Post-operation | ||
|---|---|---|---|---|
|
| ||||
| Microadenoma (n=68) | Macroadenoma (n=31) | Microadenoma (n=68) | Macroadenoma (n=31) | |
| > 200 | 35 (51.5%) | 23 (74.2%) | 3 (4.4%) | 9 (29.0%) |
| 100~200 | 20 (29.4%) | 3 (9.7%) | 1 (1.5%) | 2 (6.5%) |
| 60~100 | 8 (11.8%) | 4 (12.9%) | 3 (4.4%) | 0 (0.0%) |
| 25~60 | 5 (7.4%) | 1 (3.2%) | 6 (8.8%) | 4 (12.9%) |
| < 25 | 0 (0.0%) | 0 (0.0%) | 55 (80.9%) | 16 (51.6%) |
Postoperative menstrual improvement
In the 98 cases of irregular menstruation, 67.3% (66 cases) patients had their menstruation return to normal after operation, 23.5% (23 cases) patients had certain improvement in menstruation(including irregular menstruation after operation or need to rely on taking bromocriptine), 10.2% (10 cases) patients had no improvement in menstruation.
Influence of tumor resection degree on the improvement of menstruation
66 cases of patients who’s menstruation returned to normal after Operation, all underwent total resection. Among 88 cases of total resection, 75% had their menstruation returned to normal after operation; among 9 cases of subtotal resection, 44.4% had improvement in menstruation after operation, and the remaining failed; 2 patients of massive resection had partial menstruation improvement (Table 3). The chi-square test results showed that the menstrual improvement of total resection group was superior to those of subtotal or massive resection group (P < 0.01).
Table 3.
Relationship between the degree of tumor resection and recovery of menstruation
| Tumor resection | N | Menstruation recovery [n (%)] | ||
|---|---|---|---|---|
|
| ||||
| Return to normal | Partial improvement | No improvement | ||
| Total resection | 88 | 66 (75.0%) | 17 (19.3%) | 5 (5.7%) |
| Subtotal resection | 9 | 0 (0%) | 4 (44.4%) | 5 (55.6%) |
| Massive resection | 2 | 0 (0%) | 2 (100%) | 0 (0%) |
Influence of tumor types on menstrual improvement
76.5% patients with pituitary micro adenoma had normal menstruation after surgery; 45.1% patients with pituitary macroadenoma had normal menstruation after surgery. The chi square test showed that the menstrual recovery status of micro-adenomas was better than macro adenoma group after surgery (P < 0.01, Table 4).
Table 4.
Microadenomas and macroadenomas menstruation recovery
| Adenoma classification | N | Menstruation recovery [n (%)] | ||
|---|---|---|---|---|
|
| ||||
| Return to normal | Partial improvement | No improvement | ||
| Microadenomas | 68 | 52 (76.5%) | 12 (17.6%) | 4 (5.9%) |
| Macroadenoma | 31 | 14 (45.1%) | 11 (35.5) | 6 (19.4) |
The relationship between the preoperative level of PRL and the improvement of menstruation after operation
According to the preoperative level of PRL, the patients were divided into two groups: PRL ≥200 ng/ml and PRL < 200 ng/ml, to analyze the menstruation improvement difference between two groups after surgery (Table 5). Chi-square test results showed: preoperative PRL < 200 ng/ml group had a better menstruation status than that of the PRL ≥200 ng/ml group (P < 0.05).
Table 5.
Relationship between preoperative PRL levels and the improvement of menstruation after surgery
| Preoperative PRL levels(ng/ml) | N | Postoperative menstruation (n (%)) | |
|---|---|---|---|
|
| |||
| Normal | Partial improvement or no improvement | ||
| ≥200 | 58 | 44 (75.9%) | 14 (24.1%) |
| < 200 | 41 | 39 (95.1%) | 2 (4.9%) |
Relationship between PRL level on the first day after operation and the recovery of menstruation
Among the 71 patients who’s PRL level returned to normal on the first postoperative day, there were 83.1% (59 cases) patient’s menstruation were completely recovered, 12.7% (9 cases) were partially improved, 4.2% (3 cases) were not improved. According to the postoperative level of PRL, the patients were divided into two groups: PRL ≤25 ng/ml and PRL > 25 ng/ml, to analyze the menstruation improvement difference after operation (Table 6). Chi-square test showed that the menstruation status of postoperative PRL ≤25 ng/ml group was significantly better than that of PRL > 25 ng/ml group (P < 0.01).
Table 6.
Relationship between PRL level on the first day after operation and the recovery of menstruation
| PRL level on the first day after operation(ng/ml) | N | Postoperative menstruation (n (%)) | ||
|---|---|---|---|---|
|
| ||||
| Normal | Partial improvement | no improvement | ||
| ≤25 | 71 | 59 (83.1%) | 9 (12.7%) | 3 (4.2%) |
| > 25 | 28 | 7 (25.0%) | 14 (50.0%) | 7 (25.0%) |
The improvement of galactorrhea after operation
Among the 61 cases of patients with galactorrhea symptom, 83.6% (51 cases) had improvement after surgery while 16.4% (10 cases) failed. Among them, the galactorrhea improvement rate in micro adenoma patients was 89.7% (35/39), compared with 72.7% in macro-adenoma patients (16/22). Chi-square test showed that there was no significant difference in the improvement of galactorrhea after the operation between the micro adenoma and the macro adenoma.
Postoperative pregnancy status
We divided the group according to whether the patient married, want to give birth, and had given birth. The follow-up found that surgery can improve the fertility condition of the patients (Table 7). We found that 14 patients out of 17 infertility patients got pregnant after surgery, and 3 patients still could not. The majority of the patients were young, unmarried or did not want to pregnant.
Table 7.
Postoperative pregnancy
| Classification | The number of cases |
|---|---|
| Preoperative infertility | |
| Postoperative pregnancy | 14 |
| Postoperative still infertility | 3 |
| Preoperative and postoperative pregnancy | 6 |
| Unmarried | 57 |
| Do not want to pregnant | 18 |
| Divorce | 1 |
Discussion
The specific pathogenesis of PRL is not clear; it may be related to the high expression of cancer gene, tumor suppressor gene inactivation, or pituitary cell proliferation and other factors [11]. The treatment includes drug therapy, radiotherapy and surgery. The common treatment drug is bromocriptine, which can quickly reduce the serum levels of PRL, and reduce the tumor size, but the drug is required for long-term or lifelong medication that may leads to drug intolerance or invalid treatment [12]. Although radiation therapy has a certain effect in preventing tumor progression and the disease malignant, it cannot cure. Now, the surgical treatment is commonly used [13]. Surgical treatment includes craniotomy and transsphenoidal surgery. Craniotomy surgical treatment is a traditional and trauma operation mode, which can damage the brain easily and has more complications. So it is gradually eliminated [14]. At this point, transphenoidal surgery comes into practice and it is widely used in clinic. But there are still some problems in transphenoidal surgery. Since the pituitary is located in sellar region and the anatomical location is deep, the operation is hard to carry on and with high risk. Serious complications of hemorrhage, optic nerve injury, cerebrospinal fluid rhinorrhea, intracranial infection etc. may occur [15]. So closely nursing and observation, timely discovery of complications, and early treatment is also an important part of the rehabilitation of patients.
The whole perioperative nursing process of transsphenoidal pituitary tumor surgery required nursing staff not only to master routine nursing, but also be familiar with anatomic structure the nasal cavity and sinus area to observe the changes of the disease. The nurses need to do assessment of patients, give targeted care and assist patients do a good preparation before operation. The nursing of postoperative complication is the key point; understanding it’s mechanism. and masteringclinical manifestation is the way to find and handle the complication in time. This is very important to patients’ recovery.Psychological nursing is another important factor to patients. With the promoting of physical-psychological-social type of nursing mode [16], the psychological nursing is more and more valued in clinical care [17].
There was study noted that serum PRL was decreased to normal in the early stage after the operation of pituitary micro-adenoma [18,19]. In this study, 99 cases of female patients with pituitary PRL adenoma at child-bearing age were treated with transsphenoidal surgery and standard care. The study showed serum PRL level was reduced to normal in 71.7% patients. After operation, 66.7% patients had normal menstruation and 83.6% patients had improvement in glactorrhea, which is similar to the reports. In this study, among 88 patients with tumor total resection, 80.7% patients had PRL level drop to normal on the first postoperative day, and 75% patients had menstrual recovery. Patients having PRLreduce to normal level on the first postoperative day were all total resection cases. This situation also complied with menstruation recovery. The serum PRL level after total resection was significantly lower than that of subtotal or massive resection. This indicates that surgical resection of the tumor is an effective method for the treatment of pituitary PRL adenoma.
The objective of surgical treatment for pituitary prolactinoma is to remove the tumor as much as possible, decrease the serum level of prolactin to normal range, alleviate the symptoms of endocrine disorder or other symptoms, improve sexual function, meet the requirements of childbearing, and maintain normal pituitary function in the meanwhile. But at present, there are few reports on the fertility condition improvement after transsphenoildal surgerly in treating pituitary PRL adenoma. We found that 14 patients out of 17 infertility patients got pregnant after surgery, and it is primarily speculate that the fertility of pituitary PRL adenoma patients could be improved by transsphenoidal operation. However, patients unmarried or without pregnancy intention took a major proportion , plus lacking of a clear standard of whether pregnant, so a long-term follow-up in the future to obtain accurate results is required.
By comparing the serum level of prolactin 24 h after operation and MRI image 3 months after operation, there is a study shows that there was no significant difference between the measurement of hormone and iconographic examination regarding the diagnosis [20,21]. In our study, patients with postoperative prolactin level ≤25 ng/mL showed better recovery in menstruation than those with postoperative prolactin level > 25 ng/mL, indicating that the serum level of prolactin on the first day after operation could accurately reflect prognosis and be regarded as one of the assessment factors for surgical therapeutic effect. The effect of preoperative prolactin level on the prognosis is also the focus of the study, and it is not unified now. Tyrrell et al reported that the rate of remission was 92% for patients with preoperative serum level of prolactin < 100 ng/mL, whereas it was only 37% for patients with preoperative serum level of prolactin > 200 ng/mL [22]. Similarly, Zada et al reported that the rate of success of surgery was 75% for patients with preoperative serum level of prolactin < 200 ng/mL, and it was around 33% for patients with preoperative serum level of prolactin ranging between 200 and 600 ng/mL [23]. However, the rate of success would be none if patients had preoperative serum level of prolactin > 1400 ng/mL. On the other hand, Turner et al suggested that there was no association between prognosis of surgical treatment and preoperative serum level of prolactin [24]. In our study, the patients with preoperative serum level of prolactin ≤200 ng/mL showed better menstruation recovery than those with preoperative serum level of prolactin > 200 ng/mL. Therefore, the preoperative serum level of prolactin could be used as an indicator for postoperative improvement in the endocrine system.
In conclusion, transsphenoidal operation combining standardized nursing measures is an effective way to treat pituitary PRL adenoma, recover the fertility of partial female patients, treat the abnormal menstruation caused by pituitary PRL adenoma validly. Degree of PRL level decrease and improvement of menstruation with total removal was better than subtotal removal or massive removal obviously. In addition, the preoperative serum level of prolactin could be used as an indicator for postoperative improvement in the endocrine system. Serum level of prolactin on the first day after operation could accurately reflect prognosis, so it can be regarded as one of the assessment factors for surgical therapeutic effect [25].
Acknowledgements
The scientific research project was supported by Huashan Hospital, Fudan University (2014QD23) and Nursing Research Fund of Fudan University (FNF201024).
Disclosure of conflict of interest
None.
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