Treatment Of Prolactinomas Research Articles

Bromocriptine and cabergoline induce cell death in prolactinoma cells via the ERK/EGR1 and AKT/mTOR pathway respectively

The treatment of hyperprolactinemia is based on the use of dopamine agonists, mainly bromocriptine (BRC) and cabergoline (CAB). They reduce tumour size effectively and restore gonadal function. However, there is a difference in drug sensitivity between CAB and BRC in patients with prolactinoma, although the underlying mechanisms are still unknown. Thus, we investigated whether there are differences in tumour sensitivity to CAB and BRC and their possible differential mechanisms in two prolactinoma cell lines. In our study, we found that GH3 cells are more sensitive to BRC and that MMQ cells are more sensitive to CAB. Moreover, BRC and CAB elicited cell death via different pathways; BRC induced prolactinoma cell death mainly through the apoptosis pathway, and CAB induced pituitary prolactinoma cell death mainly via the autophagic cell death pathway. Using gene microarray analysis, we found that BRC induces the apoptosis of prolactinoma cells through the ERK/EGR1 signalling pathway, whereas CAB induces autophagic death by inhibiting the AKT/mTOR signalling pathway. Our study showed the difference in tumour sensitivity and differential mechanisms in BRC- and CAB-treated prolactinoma cells, which provides a theoretical basis for the accurate treatment of prolactinoma.

SUN-443 Surgical Management of Cystic Prolactinomas

Purpose: Treatment of prolactinomas with a predominantly cystic component remains controversial. This study assessed remission rates in surgically-treated cystic prolactinomas, compared to solid micro- and macroprolactinomas. Methods: Charts were retrospectively analyzed for 57 patients who underwent transsphenoidal resection (TSS) for prolactinomas, from 2004 to 2018, by two experienced neurosurgeons. Tumors were subdivided into: cystic prolactinomas (n=17, >50% initial cystic component), microprolactinomas (n=10, <10 mm) and macroprolactinomas (n=30, ≥10 mm). Patients underwent TSS primarily for reasons of dopamine agonist (DA) intolerance, non-responders or patient preference. Remission was defined as either immediate postoperative (POD #1-3) prolactin (PRL) level of <10 ng/dl, or a normalized PRL level at a later time point. Results: 30 females and 27 males were included in the study, with a mean age of 33.5 yrs. Median tumor size for the cystic, micro- and macroprolactinomas were 15 mm, 7 mm and 22 mm, respectively. The median duration for DA treatment for the cystic, micro- and macroprolactinoma groups, prior to TSS, were 6, 24 and 12 months, respectively. Median pre-operative PRL levels were lowest with cystic prolactinomas, compared to the micro- and macroprolactinomas at 23.9 ng/ml (Standard deviation (SD)-136.7 ng/ml), 87.9 ng/ml (SD 80 ng/ml) and 229 ng/ml (SD 471.1 ng/ml), respectively (p=0.015). Immediate post-op PRL levels were significantly lower for cystic prolactinomas (n=10, 2.65 ng/ml, SD 4.72 ng/ml) than macroprolactinomas (n=19, 57 ng/ml, SD 159.4 ng/ml) (p=0.025) and for microprolactinomas (n=9.4 ng/ml, SD 3.9 ng/ml) than macroprolactinomas (p=0.030). At the last post-op f/u, no microprolactinoma patient required DA treatment, while 4 patients (24%) with cystic prolactinomas and 18 patients (60%) with macroprolactinomas still required DA therapy. Remission was ultimately achieved in 76% (n=13/17) of surgically-treated cystic prolactinomas, 100% (n=10/10) of microprolactinomas and 23% (n=7/30) of macroprolactinoma patients, at a median f/u of 6, 2.5 and 25 months, respectively. Conclusions: Surgical treatment for cystic prolactinomas, despite their macroadenoma size, resulted in high remission rates (76%), which was comparable to surgically-resected microprolactinomas and superior to macroprolactinomas. This case series supports TSS for this subset of prolactinoma patients.

MiR-93-5p targets Smad7 to regulate the transforming growth factor-β1/Smad3 pathway and mediate fibrosis in drug-resistant prolactinoma

Prolactinoma is a common subtype of pituitary tumors. Dopamine receptor agonists are the preferred treatment for prolactinoma; however, with this therapy, drug resistance often occurs. In our previous work, we found that partial resistant prolactinomas showed increased fibrosis and that the transforming growth factor (TGF)-β1/Smad3 signaling pathway mediated fibrosis and was involved in drug resistance. Additionally, the success of surgery is known to be heavily influenced by the consistency of the pituitary adenoma. Therefore, in this study, we aimed to clarify the mechanisms of fibrosis in prolactinoma. Using high-throughput sequencing for analysis of microRNAs, we found that miR-93-5p was significantly upregulated in prolactinoma samples with a high degree of fibrosis compared with that in samples without fibrosis. Furthermore, we found that miR-93-5p was negatively correlated with the relative expression of Smad7 and positively correlated with the relative expression of TGF-β1 in clinical prolactinoma samples. In addition, luciferase reporter assays showed that miR-93-5p could downregulate the Smad7 gene, an important inhibitor of the TGF-β1/Smad3 signaling pathway, and activate TGF-β1/Smad3 signaling-mediated fibrosis in a feed-forward loop. Moreover, miR-93-5p could enhance the drug resistance of prolactinoma cells by regulation of TGF-β1/Smad3-dependent fibrosis. Taken together, our findings demonstrated that miR-93-5p may be a potential therapeutic target for inhibiting fibrosis and reducing drug resistance in prolactinoma cells.

Pituitary Disease in Pregnancy: Special Aspects of Diagnosis and Treatment?

The diagnosis and treatment of pituitary disease in pregnancy represents a special clinical challenge. Not least because there is very little data on the treatment of pregnant patients with pituitary disorders. A selective search of the literature was carried out with the aim of compiling evidence about the diagnosis and treatment of pituitary disease in pregnancy. The search covered the databases PubMed/MEDLINE including PubMed Central and also used the Livivo (ZB MED) search engine. Recent studies were evaluated for recommendations about the care of pregnant patients with hormone-inactive and hormone-active pituitary adenomas (prolactinoma, acromegaly and Cushingʼs disease), pituitary insufficiency, pituitary apoplexy and hypophysitis. The most well-established forms of treatment are for prolactinoma, due to the incidence of this disease and its impact on fertility. When pregnancy has been confirmed, prolactinoma treatment with dopamine agonists should be paused. Although microprolactinomas rarely increase significantly in size after the administration of dopamine agonists is discontinued, symptomatic tumor growth of macroprolactinomas can occur. In such cases, treatment with dopamine agonists can be resumed. If the primary tumor is large and the risk that it will continue to grow is high, it may be necessary to continue medical treatment from the start of pregnancy. If one of the partners has a pituitary disorder, it is often still possible for many couples to achieve their wish of having children if they receive medical support to plan and the pregnancy is carefully monitored. Given the complexity of pituitary disease, pregnant patients with pituitary disorders should be cared for and treated by a multidisciplinary team in centers specializing in the diagnosis and treatment of pituitary disease.

Clinical characteristics and surgical outcome of prolactinoma in patients under 14 years old.

Prolactinoma is one of the most common pituitary tumors, but relatively uncommon in patients under 14 years old. Surgery is the second-line treatment for prolactinoma when patients show resistance or intolerance to medical therapy. There are only a few published series of children who underwent surgery treatment. This study is performed to investigate the clinical manifestation and surgical outcome of pituitary prolactinoma in patients under 14 years old who are resistant or intolerant to medical therapy of dopamine agonist.Thirty-six cases were included in a retrospective review of patients under 14 years old operated for prolactinoma between December 1987 and December 2015. Preoperative radiological and endocrinal evaluation was performed on every patient. All patients received operation with trans-sphenoidal approach.Based on enhanced pituitary magnetic resonance imaging (MRI) taken 2 months after the surgery, total resection was achieved in 16 patients (44.4%) and subtotal resection in 20 (55.6%). Thirty-four cases (94.4%) showed remarkable decrease of prolactin (PRL) level 7 days after surgery, and 16 (44.4%) returned to normal. All patients were followed up for 2 years. Tumor regrowth or recurrence occurred in 5 patients and secondary treatment was applied, including drug treatment in 2 patients, second surgery in 2, and radiotherapy in 1.Trans-sphenoidal pituitary surgery is an effective treatment for prolactinoma in patient under 14 years old. There is no significant difference between the patients under 14 years old and adults for prolactinoma in characteristics and treatment.

CSF Rhinorrhea Following Medical Treatment for Prolactinoma: Management and Challenges.

Objective Cerebrospinal fluid (CSF) rhinorrhea following medical management of prolactinoma is a rare complication. We evaluated the clinical background of this condition, identify potential risk factors, and discuss the management options and challenges involved. Methodology We retrospectively reviewed clinical details of patients who were treated for CSF leaks among patients treated for prolactinoma between 2013 and 2017. Results Seven patients were treated for CSF rhinorrhea in the context of prolactinoma, with the age range between 24 and 56 years. Six patients had CSF leak following initiation of cabergoline, while one patient presented with CSF rhinorrhea. The time of onset of leak following medical treatment ranged from 14 days to 5 years. The mean preoperative serum prolactin level was 12,638 ng/mL (range: 1,000-26,287 ng/mL). All patients underwent repair of skull base defect. (four endoscopic, two microscopic, and one bifrontal craniotomy). The site of defect in the majority of patients was the sellar floor. Two patients who were initially managed with acetazolamide alone, eventually required surgical repair. Three patients were cured of CSF leak with a single procedure. Three patients had to undergo re-exploration and endoscopic repair after their first surgery failed. Two patients required lumboperitoneal (LP) shunt after a failed endoscopic transsphenoidal repair. Conclusion Surgical management for medically-induced CSF rhinorrhea is necessary; however, it can pose significant issues. Endoscopic repair of the defect should be considered at the earliest. Multiple surgical procedures are often required because of skull base erosion. LP shunt can be considered if CSF leak persists following multiple surgeries.

Does Dopamine Agonist Hormonal Therapy for Macro-Prolactinoma Affect Future Surgery?

Background: Controversy regarding first line therapy for macro-prolactinoma patients had been of debate for many decades. Several reports suggested that dopaminergic agents (DAs) medications are accused for prolactinoma fibrosis. Whether fibrosis has positive or negative influence on the management of prolactinomas is still unclear. Aim of the work: was to compare the intraoperative tumor consistency, intraoperative difficulties and complications both pre- and post-operative between macro-prolactinoma patients who received DA medications and who did not receive prior to surgery. Patients and Methods: Twenty-five macro-prolactinoma patients who underwent primary pituitary surgery, sub-labial trans-sphenoidal microscopic removal, of macro-prolactinoma grouped into two groups. Group 1 included patients who were treated by DA medication, combined therapy with Bromocreptine and Cabergoline, prior to surgery for at least 3 months. Group 2 included patients who didn’t receive any preoperative DA medications. We compared the intra-operative texture of the tumor, intraoperative and post-operative complications together with the extent of surgical excision and hormonal remission achieved. Results: No significant statistical difference as regards intra-operative tumor consistency in relation to preoperative hormonal treatment. The rate of intra-operative and post-operative complications has no relation to the pre-operative hormonal therapy by DAs nor to the intraoperative tumor consistency. The only factor that affect the extent of surgical excision is the pre-operative tumor size graded by KNOSP classification and this extent of surgical excision has direct implication on the post-operative hormonal remission rate. Conclusion: It could be concluded that there is no risk of more tumor fibrosis nor increase in the complication rate due to DA medication prior to surgery. So, using dopamine agonist as the primary treatment for prolactinoma while Surgical excision is deferred for cases of failure or intolerance of side effects of the the hormonal therapy.

Response to Cabergoline treatment in Invasive Prolactinoma with hemorrhage- A case report

Patients with invasive prolactinoma present with constellation of symptoms including headache, blurred vision, lethargy, menstrual irregularity and sexual dysfunction. Cabergoline, a potent dopamine agonist, is a known medication prescribed for the treatment of prolactinoma. Here, we report a case of invasive macroprolactinoma with hemorrhage in a 18 years female with dramatic response to cabergoline treatment clinically, biochemically, and radiologically.Jour of Diab and Endo Assoc of Nepal 2017; 1(1): 18-20

IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14years). Mean adenoma size was 23.8 ± 16.2mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

Clinical Features and Response to Treatment of Prolactinomas in Children and Adolescents: A Retrospective Single-Centre Analysis and Review of the Literature

Background: Paediatric prolactinomas are rare. The aim of this study was to investigate the clinical features and outcome of paediatric patients with prolactinomas. Methods: In this single-centre retrospective analysis, clinical, biochemical, and radiological features of all paediatric patients with pituitary adenomas diagnosed between 2000 and 2016 were evaluated. Results: Among 21 patients with pituitary adenomas, 12 patients with prolactinomas (median age 14.2 years, range 11–16.6 years, 8 females, 4 males) were identified (7 macro- and 5 microprolactinomas). The most common clinical symptoms were headaches (67%) and pubertal delay (67%). All patients with macroprolactinomas with prolactin concentrations >10,000 mU/L had at least 1 pituitary hormone deficiency. Cabergoline as first-line treatment (n = 11, median follow-up of 37 months, range 12–89 months) induced normoprolactinemia (n = 8), reduced the mean tumour volume by 80%, and ameliorated headaches (p = 0.016) and pubertal delay (p = 0.031), whereas intermittent moderate side effects occurred in 55%. Conclusion: Adolescents with headaches and pubertal delay should be investigated for prolactinomas. Treatment with cabergoline is well tolerated and effective in reducing clinical symptoms and prolactin concentrations was well as inducing tumour shrinkage. Further clinical prospective studies are needed to standardize paediatric treatment modalities.

Cabergoline-induced fibrosis of prolactinomas: a neurosurgical perspective

Presently, the standard of care for prolactinomas, a type of pituitary adenoma, is dopaminergic agents such as bromocriptine and cabergoline. However, dopaminergic agents may induce fibrosis of cardiac valves leading...

Temozolomide therapy for resistant prolactin-secreting pituitary adenomas and carcinomas: a systematic review.

Pituitary tumors represent 10-15% of all intracranial tumors; of these, prolactinomas account for 40-50% of cases. Prolactinomas usually respond well to dopamine agonists (DA) as first-line therapy. However, treatment resistance remains a concern. Temozolomide (TMZ) is an oral alkylating agent that has shown promise in treating aggressive pituitary adenomas and carcinomas that are resistant to other therapies. To date, no control trials have been undertaken and only single case reports of pituitary tumors treated with TMZ have been published. A systematic literature search was conducted for studies reporting the use of TMZ for the treatment of prolactinomas that were resistant to standard therapy. In total, 42 reported cases were identified and included in our analysis: 23 cases of prolactin-secreting adenomas and 19 of prolactin-secreting carcinomas. Prior to TMZ administration, patients had exhibited tumor progression and had previously undergone various treatments including surgery, radiotherapy, and drug therapy. Tumor shrinkage was reported in 76% of patients. Reduced prolactin levels were observed in 75% of patients, while normalization of prolactin was reported in 8%. TMZ failure occurred in 20.6% of cases. Most patients exhibited no serious adverse effects. In conclusion, TMZ has potential for the treatment of highly aggressive and resistant prolactin-secreting adenomas and carcinomas, as demonstrated by tumor shrinkage or complete response and normalization of hormone hypersecretion, and exhibits good tolerability and few side effects.

Pituitary Tumor Suppression by Combination of Cabergoline and Chloroquine.

The dopamine agonist cabergoline (CAB) has been used widely in the treatment of prolactinomas and other types of pituitary adenomas, but its clinical use is hampered by intolerance in some patients with prolactinoma and lack of effectiveness in other pituitary tumor types. Chloroquine (CQ) is an old drug widely used to treat malaria. Recent studies, including our own, have revealed that CAB and CQ are involved in induction of autophagy and activation of autophagic cell death. To test whether CAB and CQ can function cooperatively to suppress growth of pituitary adenomas as well as other cancers. In vitro studies using the rat pituitary tumor cell lines MMQ and GH3, human pituitary tumor cell primary cultures, and several human cancer cell lines showed that CQ enhanced suppression of cell proliferation by CAB. These results were confirmed in in vivo xenograft models in nude mice and estrogen-induced rat prolactinomas. To understand the mechanism of combined CAB and CQ action, we established a low-CAB-dose condition in which CAB was able to induce autophagy but failed to suppress cell growth. Addition of CQ to low-dose CAB blocked normal autophagic cycles and induced apoptosis, evidenced by the further accumulation of p62/caspase-8/LC3-II. The data suggest that combined use of CAB and CQ may increase clinical effectiveness in treatment of human pituitary adenomas, as well as other cancers, making it an attractive option in tumor and cancer therapies.

Best candidates for dopamine agonist withdrawal in patients with prolactinomas.

Dopamine agonist (DA) therapy is recommended as the first-line treatment for prolactinomas. However, it requires long treatment duration, and a high recurrence rate after DA withdrawal has been reported. We aimed to elucidate the predictors for long-term remission following DA withdrawal and propose the best candidates who can achieve complete remission after DA withdrawal. In a retrospective cohort study, we included 89 patients with prolactinoma who have withdrawn DAs with normal prolactin (PRL) levels at Seoul National University Hospital, from 2000 to 2016. Patient's data were retrieved from the electronic medical records. The median age and median treatment duration of the study patients were 33 (15-73) years and 69.5 (8.3-277.4) months, respectively. The recurrence rate after drug withdrawal was 57.3% during the 23.9 (3.0-176.8) month follow-up period. Age, gender, baseline PRL level, and baseline maximum tumor diameter were similar between the remission and recurrence group. In the Cox-proportional hazard model analysis, the significant predictors for remission were nadir PRL level of <1ng/dL (hazard ratio [95% confidence interval] = 0.37 [0.18-0.74]), invisible tumors on magnetic resonance imaging (MRI) (0.42 [0.24-0.74]), and treatment duration of >72 months (0.54 [0.30-0.96]). Of the subjects who met all the three criteria, 66.7% achieved long-term remission. Patients who have no tumor visible on MRI, have a nadir PRL level <1ng/dL during drug treatment, and received drug treatment for >6 years may be the best candidates for DA withdrawal.

Expression of Stem Cell Markers and Dopamine D2 Receptors in Human and Rat Prolactinomas.

BackgroundDopamine agonists (DAs) are the first-line treatment for prolactinomas. DAs primarily target the dopamine D2 receptor (D2R). Tumor stem-like cells (TSLCs) are associated with the tolerance to radiotherapy and chemotherapy. TSLCs have also been identified in pituitary adenomas. We aimed to characterize the expression pattern of stem cell markers and D2R in human and rat prolactinomas.Material/MethodsHuman prolactinoma specimens (n=14) were obtained from patients with surgical resection. The xenograft model of rat prolactinomas was generated by endermically injecting MMQ cells, HE and PRL were confirmed by immunohistochemical staining of tumor sections, and the expression of serum PRL was measured by ELISA. The expression of stem cell markers (CD133, Nestin, Oct4, and Sox2) and D2R in prolactinomas was detected by immunofluorescence. The proportion of CD133-expressing cells after DA treatment was evaluated by flow cytometry in vitro.ResultsWe found that a small subpopulation of cells expressing stem cell markers existed both in human and rat prolactinomas. Furthermore, the CD133-expressing cells showed negative D2R expression. Conversely, the D2R-expressing cells showed negative CD133 expression. The proportion of CD133-expressing cells in surviving tumor cells was significantly increased after DA treatment.ConclusionsOur results confirmed the existence of cells expressing stem cell markers in human and rat prolactinomas. Additionally, the CD133-expressing cells might resist DA therapy due to the lack of D2R expression.

Cerebrospinal fluid rhinorrhea in primary treatment of large and giant prolactinomas with dopamine agonists

We present a retrospective analysis of 15 patients with macropropactinomas who underwent surgery for cerebrospinal fluid rhinorrhea developed due to primary therapy with dopamine agonists at the Burdenko Neurosurgical Institute (BNI) in the period between 2005 and 2015. All patients had large and giant tumors (according to the classification adopted at the BNI). When cerebrospinal fluid rhinorrhea was detected, patients were hospitalized to the BNI for examination, detection of a CSF fistula, reconstruction of a defect, and resection (if possible) of the tumor. In the period between 2005 and 2015, 15 patients (8 males and 7 females) with prolactinomas of a large and giant size at the onset of conservative therapy underwent surgery for cerebrospinal fluid rhinorrhea at the BNI. All patients underwent transnasal reconstruction of a skull base defect, with 13 out of 15 patients undergoing simultaneous resection of the tumor. After tumor resection, reconstruction was performed using auto-fat, fascia, and glue (in 8 cases). In the remaining cases, apart from auto-fat, fascia, and glue, a mucoperiosteal flap and auto-bone were used. Fourteen patients were followe-up. In 13 cases, there was no relapse of cerebrospinal fluid rhinorrhea after skull base reconstruction. In 1 case, there was a relapse of cerebrospinal fluid rhinorrhea. Conservative treatment of patients with giant prolactinomas should be performed under regular control of ENT doctors and neurosurgeons for timely detection and surgical treatment of cerebrospinal fluid rhinorrhea.

Long-term cardiac (valvulopathy) safety of cabergoline in prolactinoma.

Background:Clinical relevance of association of cabergoline use for hyperprolactinemia and cardiac valvulopathy remains unclear.Objective:The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking cabergoline for the treatment of prolactinoma and to explore any associations with the cumulative dose of drug used.Design:A cross-sectional echocardiographic study was performed in patients who were receiving cabergoline therapy for prolactinoma.Results:Hundred (61 females, 39 males) prolactinoma cases (81 macroprolactinoma and 19 microprolactinoma) were included in the study. The mean age at presentation was 33.9 ± 9.0 years (range: 16–58 years). The mean duration of treatment was 53.11 ± 43.15 months (range: 12–155 months). The mean cumulative dose was 308.6 ± 290.2 mg (range: 26–1196 mg; interquartile range: 104–416 mg). Mild mitral regurgitation was present in one patient (cumulative cabergoline dose 104 mg). Mild tricuspid regurgitation was present in another two patients (cumulative cabergoline dose 52 mg and 104 mg). Aortic and pulmonary valve functioning was normal in all the cases. There were no cases of significant valvular regurgitation (moderate to severe, Grade 3–4). None of the patients had morphological abnormalities such as thickening, calcification, and restricted mobility of any of the cardiac valves.Conclusion:Cabergoline appears to be safe in patients with prolactinoma up to the cumulative dose of ~300 mg. The screening for valvulopathy should be restricted to those with higher cumulative cabergoline exposure.

Indications for surgical treatment of prolactin-secreting pituitary adenomas

Prolactinomas account for about 40% of all pituitary adenomas. The main treatment for prolactinomas is undoubtedly therapy with dopamine agonists (DAs). However, prolonged conservative treatment (for many years or even throughout life) that is necessary for permanent control of the disease makes some patients refuse pharmacological treatment for various reasons. In addition, not all prolactinomas respond to DAs therapy. Sometimes, the patient is not able to continue treatment because of the severity of side effects. Along with tumor resistance to therapy and patient intolerance of DAs, complications (liquorrhea, hemorrhage in the tumor) may occur during conservative treatment. In these cases, surgery is necessary. The paper analyzes the modern literature on various treatment options for prolactin-secreting pituitary adenomas and defines the indications for surgical treatment.

Cataplexy in a patient treated for prolactinoma: Case report

Introduction. Isolated cataplexy, without the presence of narcolepsy, is a relatively rare condition, and can be regarded as attacks of motor inhibition with loss of muscle tone and areflexia. The diagnosis of cataplexy relies on the clinical presentation and medical history and it is rarely confirmed by video-polygraph. We here described a female patient treated for prolactinoma who developed isolated cataplexy. Case report. A 53-year-old female treated with bromocriptine for a macroprolactinoma presented with sudden episodes of weakness and toneless legs leading to falls and injuries on several occasions. Cardiovascular evaluation was completely normal. Psychiatric evaluation showed no psychotic phenomenology or suicidal ideas. Pituitary imaging showed empty sella with a remnant sellar mass with infra- and parasellar extension. Neurological examination revealed mild obstructive sleep hypopnea/apnea. Electroencephalographic monitoring during sleep and awakening did not show appearance of epi potentials. HLA haplotyping was positive for HLADR3,16; DR51;DQ1 allele, confirming a diagnosis of isolated cataplexy. Treatment included tricyclic antidepressants and reduction of bromocriptine dosage with resolution of cataplexy. Conclusion. We reported the first case of isolated cataplexy most probably associated with dopamine agonist treatment for prolactinoma.

Surgical Outcomes of Prolactinomas in Recent Era: Results of a Heterogenous Group

Prolactinomas are primarily treated with medical therapy. Given the efficacy of dopamine agonists (DAs), surgery has remained a second-line treatment option. Despite medical therapy, some tumors display resistance and/or patients maybe intolerant of DA and require alternative treatment options. We examined the indications, efficacy, and safety of pituitary surgery for the treatment of prolactinomas. We performed a retrospective analysis of all patients who had surgery for a prolactinoma at our institution from January 1993 to October 2014. Seventy-eight patients (46 females, mean age 32 years) with a median follow-up of 12 months were analyzed. Macroprolactinomas accounted for 65% (51/78) of tumors. The most common indication for surgery in microprolactinomas was medication intolerance (37%, 10/27) and medication failure (33%, 17/51) in macroprolactinomas. DA therapy had been tried in 76% (59/78) patients prior to surgery. Following surgery, long-term remission was seen in 72% (18/25) of micro-adenomas and 20% (10/49) of macro-adenomas (32% [10/32] in those without cavernous sinus invasion). Despite persistent disease in those with macro-adenomas (34% [13/38]) were able to remain off medication. Early surgical failure was more common in males (P = .004) and those with large (P≤.001) or atypical (P = .003) adenomas. Surgery can result in prolonged remission in 72% of microprolactinomas. Despite lower remission rates among macroprolactinomas, a third of patients with persistent disease did not require medical therapy. Therefore, surgery remains an alternative effective treatment option, particularly for those who are intolerant or resistant to medical therapy. ACTH = adrenocorticotropic hormone CI = confidence interval CSF = cerebrospinal fluid DA = dopamine agonist IQR = interquartile range MIB-1 = methylation inhibiting binding protein-1 VF = visual field.