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April2013 Vol.50 Issue:      2 Table of Contents
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Long-Term Outcome of Patients with Prolactinoma

Ayman Elsayed Galhom1, Ahmed Osama2

Department of Neurosurgery1, Neurology2; Suez Canal University; Egypt


Background: Prolactinoma is the most common type of pituitary tumors. Primarily, it is treated with dopamine agonists. If medical therapy cannot be tolerated or if it fails to reduce prolactin level, surgery should be considered. Objective: To analyze the clinical and radiological findings of prolactinoma and to assess the long-term outcome of its treatment options. Methods: This is a retrospective study of 35 patients with prolactinoma (9 males and 26 females, mean age 37±2.1 years). Data were collected through medical record review, imaging examination, and patient follow-up evaluation in neurosurgery and neurology departments, Suez Canal University Hospital, from 2001 to 2011. Results: The majority of the patients had macroadenoma (65.8%), with suprasellar extension in (40%), and some degree of cavernous invasion in (20%).  Macroadenoma was present in all males (100%), while microadenoma was frequent in females (46.2%) (P<0.01). Every patient had first a trial of medical treatment with dopamine agonist. Surgeries (Trans-sphenoidal or trans-cranial) were done for 19 patients (54.3%), while 16 patients (45.7%) were continued on medical treatment. The clinical (73.9%) and radiological (94.7%) recovery of patients after surgeries were better than those of patients on medical therapy (50.0%) and (37.5%) (P=0.3 and <0.05 respectively). Conclusion: Surgery especially Transsphenoidal is more effective than medical treatment for prolactinoma, especially in micro and macro non-invasive tumors. [Egypt J Neurol Psychiat Neurosurg.  2013; 50(2): 135-141]

 Key Words: Bromocriptine, Cabergoline, Prolactinoma, Trans-sphenoidal surgeries

Correspondence to Ayman E. Galhom, Department of Neurosurgery, Suez Canal University, Egypt. E-mail:




Prolactinoma; prolactin secreting pituitary adenoma, is the most frequent pituitary tumor. It accounts for 45–66% of all pituitary adenomas, with an estimated prevalence of 62 / 100.000 individuals.1 Its clinical manifestations are caused by a virtue of its size and hormone overproduction. Prolactinoma is either microadenoma (<10 mm in diameter) or macroadenoma (>10 mm in diameter). Local mass effects may cause symptoms depending on size and extent of extrasellar extension.2 It can be presented also with hyperprolactinemia related symptoms like amenorrhea and galactorrhea in premenopausal women, and infertility and loss of libido in men.3

Options for treatment include medical therapy, surgery and irradiation. Treatment with dopamine agonists as bromocriptine and cabergoline is considered the first line of therapy. These drugs inhibit prolactin secretion and reduce tumor volume.3-6 However, in some patients intolerance to the drugs, limit their continuation. Those patients need additional treatment modalities, such as transsphenoidal surgery and/or radiotherapy.2,7

Remarkably, only very few studies have addressed the long-term follow-up of prolactinomas initially treated with dopamine agonists, including endocrine and radiological outcome.2,8,9


For further elucidation of the long term outcome of the medical and/or surgical treatment modalities of these tumors, we analyzed data for a series of patients that were treated at the Suez Canal University Hospital.




This retrospective study included 35 patients with prolactinoma. They had been treated either by: medical, surgical, or both treatments at the departments of Neurosurgery and Neurology, Suez Canal University Hospital, from 2001 to 2011.

At the entry, basal and dynamic endocrine and neuroimaging evaluations were performed for all the patients.

Normal prolactin (PRL) value was considered when the level was ≤ 20 ng/ml in females and ≤ 18 ng/ml in males. The pre-treatment PRL value was defined as the maximal value documented before the operation or medical management.

Tumor size was evaluated in early series by CT scan. Later on, high resolution MRI was done for all the patients. The maximal craniocaudal height and width of the tumor were measured on T1-weighted coronal and sagittal planes after gadolinium enhancement. Hardy classification10 was used to classify the grade and stage of the tumor. According to the last MRI obtained during prolonged follow-up, the prolactinomas were classified as residual, re-growth, recurrence, shrinkage, cystic degeneration, or no visible tumor. Tumor re-growth was defined as an increase in size of the residual tumor. Recurrence was defined as appearance of tumor mass in a patient without residual tumor mass on a previous MRI. Tumor shrinkage was defined as any decline of the tumor volume on MRI.2

Every patient had first a trial of medical treatment with dopamine agonist. However, we encountered some conditions in which we were unable to continue medical treatment in many patients (The patient refused medication, irregular medication, intolerance to the side effect of the drug, resistance of the tumor to treatment, shortage of financial supply). For those patients surgeries were performed. Different techniques of surgeries were done, depending on the various preoperative findings. The majorities of surgeries were trans-sphenoidal surgeries. In case of CSF leakage intra-operative, we used to put fat graft and gel foam early or surgical later on. If the patient had excessive CSF leakage post-operative, we added a temporary lumber drain for 2-3 days and give instruction to the patient to avoid strain.

Immune-cytochemistry was done in nearly all the patients whom had surgeries.

Patients with surgery usually stayed in the hospital for 3-5 days. Patients were followed up and examined at 3 and 6 months after surgery for one year then yearly thereafter. Follow up ranges from three month up to five years in some cases. Patients with conservative treatment had the same sequence of follow up time in the outpatient clinics. They were initially treated with dopamine agonists, starting with 2.5 mg/day for bromocriptine and 0.5 mg/week for cabergoline, and dose titration was based on the clinical response and serum PRL level. The treating physician had the possibility to switch the drugs.

The follow-up data included; symptoms of hyperprolactinemia, dopamine agonist therapies, hormonal replacement therapies, and intervening treatments (another operation or radiation therapy for residual or recurrent tumor). The postoperative PRL value was the lowest value documented after long term follow up. Patients who had normal PRL values, demonstrated no further symptoms or signs, reported no further subsequent therapy during follow-up evaluation, and had no residual or recurrent mass were considered to be “Cured”. Patients who still exhibited improvement in the clinical, hormonal and radiological data were considered to be in a “Regressive remission” state. If the patients experienced no more improvement with hyperprolactinemia, they were considered as having a “Persistence of disease”. If they had more progression of the clinical, hormonal, and radiological data, they were considered as having a “Progressive disease”. Resistance to medical treatment was defined as failure to achieve normal PRL levels and/or a reduction of 50% or more in tumor size by dopamine agonists.

Statistical Analysis

SPSS for Windows version 14.0 (SPSS, Inc., Chicago, IL) was used to perform data analysis. Data were expressed as the mean ±SD, unless otherwise mentioned. Subgroups were compared by Chi-square tests, when appropriate. Differences were considered statistically significant at P<0.05.




Thirty five patients were included in the study. They were 26 females (74.3%) and 9 males (25.7%). The mean age was 37±2.1 years (Range 18-65 years). Table (1) shows symptoms and signs of hormonal disturbance and mass effects with variable degree of visual field defects of the patients. One of the patients had history of previous surgery not in our hospital.

Table (2) shows serum PRL levels of the patients. Thirty four patients (97.1%) had serum PRL level ≥ 200 ng/ml. The higher PRL level tended to present more in males (66.7%) than in females (61.5%). Some hormones were deficient in some patients [Growth hormone (2.9%), Testosterone (5.7%), Estradiol (2.9%), ACTH and Cortisol (5.7%) and TSH, T3 (5.7%)]. The highest hormonal deficiencies occurred in the middle age patients. One of the patients (2.9%) had associated higher growth hormone level.    

Table (3) shows Grade and Stage of prolactinoma of studied patients. The majority of the patients 23 (65.7%) had macroadenoma and 12 patients (34.3%) had microadenoma. Fourteen patients (40%) had sellar and suprasellar extension. Cavernous invasion had been reported in 7 patients (20%). Significantly, macroadenoma was presents in all males, while microadenoma was frequent in females (46.2%) with p-value of <0.01. High PRL level was more frequent with high tumor grade (P<002).

Surgery was done for 19 patients (54.3%). The transsphenoidal approaches were performed for 16 patients; sublabial for 4 patients (11.4%) in early study; and endonasal (microscopic or endoscopic) for 12 patients (34.3%) later on (Figure 1). Transcranial surgeries were implemented in 3 (8.6%) patient (Figure 2). Sixteen patients (45.7%) continued on medical treatment, including one with previous surgery (Figure 3).

We experienced some complications during and after surgeries of the 19 patients. During operation: there were 2 patients (10.5%) with excessive bleeding; one of them had a cavernous invasion of the tumor. They needed packing with gel foam and surgical. Both developed diabetes insipidus (DI) and one developed panhypopituitarism due to hemorrhage within the tumor bed later on. Furthermore, transcranial surgeries were done for three patients (15.8%) with one case with optic nerve injury with no recovery.

CSF leakage was experienced in 4 patients (21%) that mandated a fat grafts and two of them required lumbar drain. Comparable to the pre-treatment hormonal deficiencies for patients with conservative and surgical managements; 3 patients (8.6%) developed deficiency of T4, 2 patients (5.7%) developed deficiency of cortisol, and one patient (2.9%) developed panhypopituitarism. The hormonal deficiencies were more frequent in the surgical than in the conservative group (P<0.004). However, dopamine agonist therapy was continued for all the patients in the conservative group, while it was continued for only 6 patients (31.5%) in the surgical group (P <0.001). Diabetes insipidus was present in 4 patients (21%); 1 patient (5.25%) had transient deficiency for 4 week, 2 patients (10.5%) required treatment for 1-8 months, and one (5.25%) requires live long anti diuretic hormone (ADH) therapy (Table (4).

The diagnosis of prolactinoma was confirmed in 17 patients (48.6%). Three tumors (8.6%) were invasive. The invasive prolactinoma tend to occur more frequent in males (22.2%) than in females (3.8%). However the difference was statistically non-significant (P=0.07).

Clinically cured patients were 22 (62.9%).  Regressive remission patients were 10 (28.6%), and 3 patients (8.6%) had persistence course with medical treatment. Various degree of visual, hormonal, and radiology recoveries are shown in Table (5).

The clinical and radiological recovery; of patients after surgeries were better than those on medical therapy (P=0.3 and =0.013, respectively). The discrepancy between clinical and radiological findings can be attributed to the remission of the clinical symptoms and sign is not as frequent as those with radiological findings.

In the conservative group, Cabergoline showed better treatment response than Bromocriptine in the cured and regressive remission patients (31.4% versus 22.9%), including patients who had no response to bromocriptine at the start of treatment and did for cabergoline (5.7%). However the difference was statistically non-significant (P=0.28) (Table 6).

Recovery and regressive remission were higher among patients with low level of pre-treatment PRL and low-grade tumor in both treatment groups (P=0.1 and P=0.07 respectively).

The overall normalization of serum PRL level with treatment (medical or surgical) was 30 patients (85.6%). It represents 18/19 (94.7%) of the surgical group comparable to 12/16 (75%) of conservative one. We have two recurrence cases (10.5%) in the surgical group. They were treated conservatively with good response. In the conservative group, one patient (6.25%) had recurrence after surgery done elsewhere and treated medically in our hospital. This patient had conventional radiation in addition to medical treatment with good response. In conservative group, we have more 4 (11.4%) patients whom had elevated serum prolactin with no true actual recurrence on follow up MRI.


Table 1. Clinical Manifestations of the patients (n=35).


Clinical manifestation

n (%)

Clinical manifestation

n (%)







Blurring of vision                  


Amenorrhea ± Galactorrhea


Loss of the peripheral field  


Decrease libido ± Failed erection


Decrease vision in both eyes






Acromegalic features                


Bilateral superior temporal  




Blind one eye, hemianopia of other  


History of apoplexy                 


Bilateral Constricted field 




Associated third nerve              


* Females, ** Males, ***Patients with visual field defect


Table 2. Serum prolactin level of the patients (n=35).


Prolactin level

n (%)

100 - <200                               

1 (2.9%)

200 - <500                            

12 (34.3%)

500 – 1000                             

5 (14.3%)

1000 - <2000                         

9 (25.7%)


8 (22.9%)


Table 3. Prolactinoma Grade and Stage (n=35).



n (%)


n (%)


12 (34.3%)


4 (11.4%)


18 (51.4%)


2 (5.7%)


3 (8.6%)


1 (2.9%)


2 (5.7%)


1 (2.9%)


35 (100%)

A, E                                        B, E                                        C, E

2 (5.7%)

3 (8.6%)

1 (2.9%)


14 (40%)


Table 4. Operative and Post-operative complications (n=19).



n (%)

Excess bleeding                           

2 (10.5%)

Optic nerve injury                       

1 (5.25%)

Graft with CSF Leakage            

4 (21%)

Hormonal replacement

13 (37.2)


Short up to one month               

Intermediate up to one year     

Lifelong for years                   

4 (21%)

2 (10.5%)

1 (5.25%)

1 (5.25%)

DI Diabetes insipidus, ADH Antidiuretic hormone


Table 5. Long term Outcome (n=35).


Prolactin Outcome

n (%)

Normal with no treatment

17 (48.6%)

Normal with treatment               

13 (37.1%)


5 (14.3%)

Clinical Outcome

n (%)


22 (62.9%)


10 (28.6%)

Radiological Outcome

n (%)

No visible tumor                          

26 (74.2%)


1 (2.9%)


5 (14.3%)


2 (5.7%)


Table 6. Medications for Prolactinoma (n=35).



n (%)


7 (20%)


8 (22.9%)

Bromocriptine then Destinox  

6 (17.1%)

Destinox then Bromocriptine  

2 (5.7%)

No medication                      

12 (34.3%)




Figure 1. A) MRI T1-wieghted image with contrast pre-operative of 25 years old female with progressive deterioration of vision more on the left eye and irregular menstruation. B) One year after surgery shows relieve optic nerve, left deviation of pituitary stalk with residual functioning gland.




Figure 2. A) MRI T1-wieghted image preoperative 55 years old male with progressive deterioration of vision and erectile dysfunction. B) He had trans-cranial surgery with decompression of the optic nerve and preservation of the stalk and gland.




Figure 3. A) MRI T1-wieghted image 23 year old female with macroprolactinoma with visual impairment. B) Two years after treatment with marked visual improvement and tumor remission. 





Although most patients with prolactinoma have decrease level of PRL after operation, only 40 to 70% of the patients will be cured, with long-term postoperative PRL levels in the normal range11-13. Normal PRL values were achieved in range from 66 to 96%.14,15 In these studies, normalization of PRL reported more frequently than mass remission itself7,14-16, which in fact widened the spectrum of cured rate. In our series, we found that the results lie in each group; 62.9% of the patients were completely cured, and this result rose to 85.6% when we used normalization of PRL as a curative marker.

Microprolactinoma has a benign course and rarely increasing in size with time, while macroprolactinoma can behave as highly invasive tumor, especially in men.17 Males are greater than tenfold increased risk of harboring an aggressive prolactinoma than females, probably, due to delay in diagnosis in males, greater tumor proliferative potential, more vascular macroadenoma and more cellular atypia.17-19 In our series, macroadenoma is presents in all males compared to 53.8% in females (P<0.04) and higher PRL level tends to present more in males (66.7%) than in females (61.5%) (P<0.019).18,20 However, dopamine agonist therapy can achieve PRL normalization regardless of tumor size in most men with prolactinoma.20

The study proved with others4,9,16 that there is a close correlation between the size of the prolactinoma and serum prolactin levels (P=0.002). Furthermore, a lower outcome is noticed with high grade tumor but the difference was statistically non-significant (P=0.075).11,20

Surgery can be used as a second line treatment for macroprolactinoma. Surgeries (transsphenoidal or less transcranial) were considered necessary as a second line therapy in 54.3% of the patients because of resistance to dopamine agonists. In previous studies surgery was used as a second line treatment in 14–38% of the patients.2,16 This study has relative high level of surgeries due to high level of drugs resistance.

The recurrence rate was varied according to follow up, in studies with long term follow up with small sample size ranges from 4-17%.2,21 The recurrence rate in the study cases were 5.7%. The incidence of Diabetes insipidus reported in 21%. The incidence of a temporary diabetes insipidus ranges from 10% to 40%.11

Therapy with dopamine agonists such as bromocriptine, cabergoline, and quinagolide  have proven to be highly effective treatment for prolactinoma, both in rapid reducing hyperprolactinemia and inducing tumor shrinkage within 3 months of therapy in the majority of tumors.2,3,5,7,15 Clinical improvement is often obtained with serum PRL normalization in 70–80% of the patients, and tumor shrinkage in about 80% of macroadenomas. However, one of the drawbacks is the need for long-term therapy. In fact, there are some studies that show maintenance of normoprolactinemia and absence of adenoma re-expansion after Bromocriptine or Cabergoline withdrawal in patients on long-term treatment for prolactinomas.2,4-6 In the present study  Cabergoline showed better treatment response than bromocriptine (31.4% versus 22.9%) but it is not statistically significant (P<0.28). Despite of cabergoline has been shown to be effective in normalizing PRL levels in some macroprolactinomas resistant to other agents, approximately 25% of these resistant tumors still do not achieve PRL normalization when standard maximal doses are used.22



In conclusion, prolactinoma is a common pituitary tumor. The majority of prolactinoma patients in the study are macroadenoma. Male presented with higher PRL level, higher tumor grade and more aggressive tumor behavior than female. The surgical outcome is superior to medical long term outcome in treatment of prolactinomas. In the surgical group, outcome is better in low grade and less invasive tumors. In the conservative group, the medically treated group cabergoline shows better outcome than bromocriptine. However, medical treatment should be tried in every patient.


[Disclosure: Authors report no conflict of interest]




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الملخص العربى


المتابعة طويلة الأمد لنتائج علاج مرضى أورام الغدة النخامية المصحوبة بإفراز هرمون البرولاكتين


الخلفية: يعد ورم هرمون البرولاكتين من أكثر أورام الغدة النخامية شيوعا. وكثيرا ما يعالج بمحفزات الدوبامين. وإذا تعذر تحمل المريض للعلاج الدوائي أو لم تنخفض مستويات  الهرمون بالدم فان الجراحة تعد الخيار التالى. الأهداف: وقد تم إجراء هذا البحث بهدف تحليل النتائج الإكلينيكية ونتائج فحص الأشعة لمرضى ورم هرمون البرولاكتين وأيضا لتقييم نتائج بعيدة المدى لوسائل علاج هؤلاء المرضى (الجراحية والدوائية). طرق البحث: وقد شمل البحث على 35 مريضا (9 رجل و 26 امرأة, ومتوسط العمر 37 ± 2.1 عاما) تم علاجهم بأقسام جراحة المخ والأعصاب والأمراض العصبية بمستشفى جامعة قناة السويس. النتائج: خضع كل مريض أولا للعلاج بمحفزات الدوبامين. معظم المرضى كان حجم الورم اكبر من 1 سنتيمتر بنسبة 65.8%، ويمتد الى فوق السرج التركي بنسبة 40% كما قدر من غزو الجيب الكفى بنسبة 20%. وقد لوحظ أن حجم الورم اكبر من 1 سنتيمتر موجود في جميع الذكور (100%), بينما كان الحجم الأقل من 1 سنتيمتر أكثر شيوعا في النساء بنسبة 46.2%. وكان ذا دلالة إحصائية عالية. وقد تمت العمليات الجراحية من أعلى أو عبر الأنف على 19 مريضا (54.3%) بينما 16 مريضا (45.7%) واصلو العلاج الدوائي. وكانت نسبة المرضى الذين تحسنوا من الناحية السريرية (73.9%) أو بالأشعة (9. 97%) بعد العمليات الجراحية أفضل من العلاج الدوائي (50%) و (37.5%)على الترتيب. والخلاصة: أن الجراحات الدقيقة خاصة عبر الجيب الانفى لأورام هرمون البرولاكتين أجدى من العلاج الدوائي.


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