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Introduction: Prolactinomas are unique tumors that may go into both hormonal and radiographic remission with dopamine agonist therapy or transsphenoidal surgery. Regardless of modality, the goals of therapy remain the same: (1) biochemical remission, including reduction of prolactin and normalization of sex hormones; (2) radiographic tumor control, with a range including prevention of tumor growth, tumor regression, or complete tumor resolution; (3) resolution of preoperative symptoms, including those that are hormonal or neurologic; and (4) prevention of new hypopituitarism or new neurologic symptoms., Areas Covered: In the following review, we performed a search of the literature using keywords 'prolactinoma,' 'dopamine agonist,' 'surgery,' 'cost-effectiveness,' 'recurrence,' and 'complication' to compare the relative merits of medical versus surgical therapy for prolactinoma, including special circumstances such as cystic tumors, pregnant patients, and the cost-effectiveness of different strategies., Expert Commentary: Medical therapy can offer a cure, but surgery provides an important adjunct to patients with resistance or intolerance to dopamine agonists, and offers excellent outcomes including when combined with continued postoperative medical therapy. Further head to head comparisons will benefit patients and practitioners weighing the relative risks and benefits of medical and surgical intervention, including the issue of their relative cost-effectiveness.

The impact of sexual dysfunction (SD) is distressing to many male patients with pituitary adenomas which affect both physical and psychological health. The research explored to identify risk factors affecting sexual function and the prognosis of male patients with pituitary adenomas. Two hundred and fifty-four male patients, who aged between 18 and 60 (mean ± s.d.: 44.16 ± 10.14) years and diagnosed with pituitary adenomas, were retrospectively analyzed. One hundred and fifty-nine patients (62.6%) complained of SD prior to surgery. The mean International Index of Erectile Function (IIEF-5) in patients with giant adenomas was 16.13 ± 2.51, much smaller than those with microadenomas or macroadenomas (P < 0.05). All the patients showed significant improvement in terms of erectile dysfunction (ED) following surgery (P < 0.05). In addition, complete resection achieved a higher degree of SD relief than partial resection. The incidence of SD in functioning pituitary adenomas (FPAs) was much higher than that in nonfunctioning pituitary adenomas (NFPAs) (P < 0.05). In addition, compared with NFPAs, males with prolactinomas (82.8%) had the higher prevalence of SD and significantly improvement following surgical intervention (P < 0.05). An inverse relationship was identified between decreasing testosterone levels and increasing incidence of SD before surgery (P < 0.05). There was no significant difference between 6 months and 12 months after surgery in serum testosterone level (P > 0.05). Our results indicated that surgical therapy could be optimized for improvements in SD and that testosterone levels can be used as a sensitive indicator to predict the recovery rate of sexual function in patients with pituitary adenomas following surgery and the serum testosterone level will stay stable in 6 months after surgery.

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 to valvular insufficiency, necessitating surgical treatment of prolactinoma. Fibrosis of prolactinoma can be induced by prolonged medical treatment with bromocriptine, and this usually occurs after years of treatment. In comparison to bromocriptine, there have been no reports of cabergoline-induced fibrosis of prolactinoma. There is a potential for greater emphasis to be placed on assessing the tumour consistency from preoperative MRI scans, or even preoperative contrast-enhanced 3D Fast Imaging Employing Steady-state Acquisition imaging to allow better planning of the surgery. We report a rare case of fibrosis of prolactinoma after cabergoline treatment resulting in its subsequent difficult surgical removal. This patient had early MRI changes of fibrosis of prolactinoma after a short period of 6 months of cabergoline treatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Radiographic detection of calcification in pituitary adenoma is relatively rare, and the clinical characteristics of pituitary adenoma with calcification remain unclear. Herein, the clinical characteristics of pituitary adenoma with radiological calcification were investigated., Methods: A total of 160 patients who underwent surgical resection of pituitary adenomas between February 2004 and December 2016 were reviewed. Eighty-one patients had hormone-secreting pituitary adenomas, and 79 patients had nonfunctioning pituitary adenoma. Among these 160 patients, cases with radiological calcifications on preoperative neuroimaging were included in this study, and clinical characteristics with intraoperative findings were analyzed, retrospectively., Results: Pituitary adenoma with calcification on preoperative neuroimaging was observed in only nine cases (5.6%). The study population consisted of these nine patients with nonfunctioning pituitary adenoma (n = 5), mixed growth hormone and prolactin-secreting pituitary adenomas (n = 3), and a prolactinoma (n = 1). In 89% of cases (n = 8), calcified pituitary adenoma was soft enough for suction despite the presence of a granular gritty texture intraoperatively. Besides, in a single patient (11%), evidence of hard thick capsular calcification was seen surrounding a soft tumor component; however, it did not interfere with adequate removal of the soft part, and tumor resection was possible in all cases without any complications., Conclusions: Pituitary adenoma presenting with calcification is relatively rare, but should be kept in mind to avoid making a wrong preoperative diagnosis. As not all pituitary adenomas with calcification are hard tumors, preoperative radiological calcification should not affect decision-making regarding surgical indications.

The natural history of giant prolactinomas is not known. While it is commonly accepted that the enlargement of microadenoma is rare and more limited than macroadenoma, it is so far uncommon that macroadenoma progress to giant adenoma. Thus, spontaneous enlargement of adenomas is poorly documented. We report the unusual history of undiagnosed microprolactinoma, revealed 12years later at the stage of a giant adenoma presenting as a skull base tumor. This unique observation provides information on the natural history of giant adenomas and arguments for particular attention to microadenomas with signs of invasion. Moreover, this clinical case highlights the need for a prolactin dosage for all midline skull base tumors., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: Pituitary surgeons frequently encounter female prolactinoma patients seeking treatment to restore fertility. Current medical guidelines recommend using dopamine agonist (DA) for this, but for fetal safety, DA should stop upon pregnancy confirmation. The probability that prolactinoma may grow during pregnancy makes this last recommendation imperfect. With the advances in endoscopic surgery, we queried the potential role for surgery in these infertile patients, who may be ambivalent about both stopping and continuing DA while pregnant., Methods: An anonymous survey was sent to pituitary surgeons to investigate how they would advise prolactinoma patients on treatment of infertility, and counsel them about pregnancy. Directories from various US-based neurosurgical societies were culled. Surgeons who designated themselves as "skull base"/"pituitary" were surveyed., Results: Seventy-six surgeons responded (41%). The majority (67%) adhered to medical guidelines for microprolactinoma, but 26% recommended surgery. However, for a macroprolactinoma at diagnosis, the number of surgeons who recommended DA treatment vs. surgical treatment were almost evenly split (χ 2 p=0.06). The practice setting of a multidisciplinary clinic with endocrinologists did not significantly influence our respondents' choice. For a patient who presented after becoming pregnant on DA, our respondents were against surgery to prevent tumor growth (96%)., Conclusion: A review of the current literature shows that both medical and surgical therapy have flaws. Significant numbers of surgeons considered surgery a legitimate option for prolactinoma patients seeking to be pregnant. The divergence between these surgeons' opinion and current medical guidelines warrants further investigation and discussion., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Cavernous sinus (CS) tumors often are considered inoperable. We present our experience with endoscopic endonasal surgery (EES) and compare the outcomes for different tumor., Methods: EES (medial or lateral approach) was used in 234 patients with CS tumors. The cohort included 175 (75%) pituitary adenomas and 59 (25%) nonadenomatous lesions., Results: Presenting symptoms were significantly different between the 2 groups, with cranial neuropathies occurring mainly in nonadenomas (P < 0.0001). The overall gross total tumor resection rate from the CS was 37.3% (37.1% in adenomas, 38.1% in non-adenomas). In total, preexisting cranial nerve (CN) dysfunction improved in 56.4% of the patients. After treatment completion (including radiation of residual tumor), 83.3% of acromegalic patients, 50% of prolactinomas and 33.3% of Cushing's disease, were in remission. Visual loss improved in 86.8% of adenomas and in 70.8% of nonadenomas. Intracavernous CN palsies improved in 77.3% of adenomas and 42.4% of nonadenomas. New permanent CN palsies occurred in 7 nonadenomas, which is significantly greater than in adenomas (P = 0.007). The leak rate of cerebrospinal fluid was 6.3% for adenomas and 11.9% for nonadenomas. Four patients suffered an internal carotid artery injury with no neurologic sequelae in 3 cases and 1 death (0.4%)., Conclusions: EES provides an easily accessible midline corridor to the CS with equivalent or superior results to transcranial approaches in the management of select tumors. Symptomatology due to CS invasion is more likely to improve in pituitary adenomas and the rate of surgical complications is greater in nonadenomas. Using a team approach, the overall mortality due to vascular injury is low., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Medical therapy with dopamine agonist is very effective in controlling prolactin serum levels and it usually represents the first therapeutic choice for prolactin secreting pituitary adenomas. However, many patients present increase of prolactinemia after withdrawal of medical therapy which consequently should be taken for long time; other present intolerance to medical therapy; women with pregnancy need to withdraw dopamine agonists with consequent potential related problems: in these patients transsphenoidal surgery can be requested. The presented study concerns the efficacy of transsphenoidal surgery in patients affected by microprolactinoma after treatment with medical therapy for different periods of time. Different postsurgical results were achieved in 2 groups of 24 (group 1) and 25 (group 2) patients affected by microprolactinoma who had taken medical therapy for a period of time respectively longer or shorter than 1 year. In summary, the authors observed in group 1 a rate of hormonal remission of 33.3% and an overall prolactinemia improvement with possibility of medical therapy withdrawal in 49.9% of patients. In group 2, the authors observed a rate of hormonal remission of 84% and an overall rate of improvement with no necessity of medical therapy of 92%. Therefore, the authors' experience showed that the surgical option for the therapy of microprolactinomas should be indicated within 1 year from the beginning of medical therapy with dopamine agonist, to achieve a high rate of hormonal remission and possibility to withdraw medical therapy. The authors' protocol for microprolactinoma treatment is presented.

Prolactinomas account for ∼40% of all pituitary adenomas and are important causes of infertility and gonadal dysfunction. In general, most prolactinomas are treated medically with dopaminergic agonists, while surgery is reserved for patients intolerant or nonresponsive to these medications. The aim of this study was to carry out a comparative analysis of the cost-effectiveness of medical therapy with bromocriptine and surgical therapy with trans-sphenoidal surgery. A Markov model was developed based on retrospective data from 126 patients with prolactinoma treated in our hospital between October 2008 and May 2009, and from data published previously. For patients with microadenoma, the cost of medical treatment was estimated to be ¥20,555, while the cost of surgery was calculated to be ¥22,527. For patients with macroadenoma, the cost of therapy with bromocriptine was ¥31,461 in males and ¥27,178 in females, while the cost of surgery was ¥42,357 in males and ¥44,094 in females. Sensitivity analyses (carried our using variations in patient age, bromocriptine therapeutic dose, bromocriptine maintenance dose, and the success rate of bromocriptine withdrawal) indicated that our model showed good stability, although our results were most heavily influenced by variations in the bromocriptine maintenance dose. It is concluded that, from an economic viewpoint, medical therapy with bromocriptine should be the first-line treatment option for patients with prolactinoma, irrespective of whether this is a microadenoma or macroadenoma.

Background: Pituitary adenoma (PA) is a benign primary tumor that arises from the pituitary gland and is associated with ophthalmological, neurological and endocrinological abnormalities. However, causes that increase tumor progressing recurrence and invasiveness are still undetermined. Several studies have shown N-myc downstream regulated gene 2 (NDRG2) as a tumor suppressor gene, but the role of NDRG2 gene in pituitary adenoma pathogenesis has not been elucidated. The aim of our research has been to examine NDRG2 mRNA expression in PA and to determine the associations between the NDRG2 gene epigenetic changes and the development of recurrence or invasiveness of PA and patient clinical data., Methods: The MS-PCR was used for NDRG2 promoter methylation analysis and gene mRNA expression levels were evaluated by qRT-PCR in 68 non-functioning and 73 functioning adenomas. Invasiveness was evaluated using magnetic resonance imaging with Hardy's modified criteria. Statistical analysis was performed to find correlations between NDRG2 gene mRNA expression, promoter methylation and patient clinical characteristics and PA activity., Results: The NDRG2 mRNA expression was significantly lower in the case of acromegaly (GH and IGF-1 hypersecretion) than in other diagnoses of PAs (p < 0.05). Also, the NDRG2 expression was significantly higher in prolactinoma (PRL hypersecretion) than in in other diagnoses of PAs (p < 0.05). The promoter of NDRG2 was methylated in 22.69% (12/58 functioning and 15/61 non-functioning) of patients with PA. However, the NDRG2 gene mRNA expression was not significantly related to its methylation status. Clinical factors, such as: age, gender, relapse and diagnoses of Cushing syndrome were of no significance for NDRG2 promoter methylation and mRNA expression levels, as well as secreting or non-secreting PAs and the invasiveness of PAs., Conclusion: The different NDRG2 promoter methylation and expression levels in PA samples showed tumor heterogeneity and indicates a potential role of this gene in pituitary adenoma pathogenesis, but the corresponding details require intensive research.

Purpose: It is generally accepted that dopamine agonists (DA) represent the first-line treatment for most patients with prolactinoma, and patients become candidates for surgical intervention when DA is contraindicated. Surgical indication for cystic prolactinoma remains controversial. This study was performed to investigate the significance of surgery for cystic prolactinoma., Methods: A total of 28 patients that underwent transsphenoidal resection of prolactinoma between February 2004 and May 2016 were reviewed. Five consecutive patients with cystic prolactinoma were included in this study. Our surgical strategy for cystic prolactinoma was categorized as follows: first, when the purpose of surgical resection was normalization of the prolactin level, aggressive resection was performed; second, when volume reduction was essential to relieve the visual symptoms and headache, internal decompression was performed followed by DA therapy. The clinical outcomes were analyzed accordingly., Results: All cystic prolactinoma were resected via the transsphenoidal approach without any complications, and all symptoms including visual impairment and hypogonadal activity were finally relieved combined with medication., Conclusions: Surgery for cystic prolactinoma could be a better option. Transsphenoidal surgery is relatively safe to remove the cystic prolactinoma, additionally it can normalize the prolactine level and achieve adequate and rapid decompression of optic chiasm. The risk of transsphenoidal surgery is highly dependent on the skill of the surgeon and treatment decision for cystic prolactinoma needs to be individualized for each patient.

We report a 28-year-old woman who presented with a 6-year history of milk-like discharge from both of her nipples and was diagnosed with prolactinoma based on computed tomography (CT) findings and serum prolactin level. Further breast examination revealed a mass located in the upper outer region of the left breast. She underwent subtotal pituitary tumor resection. Thereafter, modified radical mastectomy was performed for left breast cancer. Twelve years after treatment, prolactinoma recurrence was detected, and bromocriptine therapy was administered. No recurrence of breast cancer was discovered. Based on this case report, we stress the importance of prolactin levels due to their possible biologic effects on breast cancer induction or growth.

A total of 184 cases of surgically treated male prolactinoma were analyzed retrospectively to summarize the outcome of this surgical intervention. We analyzed the general characteristics, clinical manifestations, hormone levels, imaging features, preoperative treatments, surgical outcomes, pathology results, and follow-up records for all included patients. The most common clinical manifestations included sexual dysfunction (47.4%), headache (55.9%), and visual disturbance (46.7%). Serum prolactin levels ranged from 150 to 204,952 ng/mL. Tumor size varied from 6 to 70 mm. Pituitary adenomas grew in a parasellar pattern with visual deficits occurring 40.7% of the time. After surgical therapy, 88.6% of patients achieved symptom relief, and 98.4% experienced an immediate postoperative decline in prolactin level. Fifty-seven patients (31.0%) achieved initial remission, and 26 patients (45.6%) experienced recurrence. Hence, our results suggest that in male prolactinoma characterized by a large pituitary diameter and high serum prolactin level, tumor size predicts the degree of gross resection. The prognostic predictors included preoperative tumor growth pattern and Ki-67 index.Citation: Yi-jun S, Mei-ting C, Wei L, Bing X, Yong Y, Ming F, Ren-zhi W. (2016) Surgical treatment for male prolactinoma: a retrospective study of 184 cases., Competing Interests: The authors have no funding and conflicts of interest to disclose.

While dopamine-agonists are the first-line approach in treating prolactinomas, surgery can be considered in selected cases besides non-responders or patients with dopamine-agonist intolerance. The aim of the present study was to compare the long-term outcome in women with prolactinomas treated primarily either surgically or medically who had not had prior dopamine-agonist treatment. Retrospective case-note study of all consecutive women with prolactinomas primarily managed with medical therapy or surgery in a tertiary referral centre. The clinical, biochemical, and radiological responses to first-line treatment at early and long-term follow-up were analysed. The primary therapeutic strategy was dopamine-agonists for 36 (34 %) and surgery for 71 (66 %) of the women. Baseline clinical and biochemical characteristics were not significantly different between the primary surgical and medical cohort. Median follow-up time was 90 months (range 13-408). Following primary treatment, prolactin level significantly decreased in both cohorts, on average to 13.5 µg/L (IQR 7-21; p < 0.001), and was within the normal range in 82 % of all patients. No women in the surgical cohort demonstrated permanent sequelae and morbidity was low. At final follow-up, control of hyperprolactinaemia required dopamine-agonist therapy in 64 % of women who had undergone primary medical therapy vs. 32 % of those who had primary surgical therapy (p = 0.003). Logistic regression revealed that the primary therapeutic strategy, but not adenoma size, was an independent risk factor for long-term dependence on dopamine-agonists. The present data indicate that in a dedicated tertiary referral centre, long-term control of hyperprolactinaemia in women with prolactinomas is high. In selected cases, a primary neurosurgical approach might at least be interdisciplinarily discussed with the primary goal of minimizing long-term dependence on dopamine-agonists.

Background: The purpose of this study was to compare the surgical efficacy of the microsurgical sublabial approach (MSA) versus the endoscopic endonasal approach (EEA) for the treatment of pituitary adenomas, based on short-term (12 months) radiological and endocrinological follow-up., Methods: One hundred and fourteen patients affected by pituitary adenoma were enrolled at our Unit between January 2007 and February 2012; 72 were treated with MSA, and 42 with EEA. The preoperative parameters considered were: type of lesion (secreting or nonsecreting), lesion size, presence of intralesional hemorrhage, lesion perimeter (nodular vs. uniform), intrasellar vs. suprasellar, involvement of cavernous sinus, and osteodural infiltration. Hormonal assays and magnetic resonance imaging (MRI) scans were performed at 12 months after the surgical procedure., Results: Univariate analysis of the data documented a statistically significant difference in favor of MSA for the subgroups of secreting adenomas (90.9 % vs. nonsecreting 48.3 %), microadenomas (100 % vs. macroadenomas 57.1 %), adenomas without osteodural infiltration (87.5 % vs. 55.5 % with the infiltration) or those without intralesional hemorrhage (75 % vs. 45.9 % with the hemorrhage), and growth hormone (GH) adenomas (88.8 % vs. 43.7 %). Multivariate analysis confirmed the greater effectiveness of MSA for the treatment of micro-secreting adenomas., Conclusions: Recent advances in the EEA for treating pituitary adenomas could lead to this modality replacing the microsurgical technique. In our experience the MSA allowed us to achieve better results in the treatment of microadenomas.

Background: Primary lactotroph disinhibition, or stalk effect, occurs when mechanical compression of the pituitary stalk disrupts the tonic inhibition by dopamine released by the hypothalamus. The resolution of pituitary stalk effect-related hyperprolactinemia postoperatively has not been studied in a large cohort of patients. We performed a retrospective review to investigate the time course of recovery of lactotroph disinhibition after transsphenoidal surgery., Methods: Medical records were retrospectively reviewed for all patients undergoing transsphenoidal surgery with the senior author from April 2008 to November 2014., Results: Of 556 pituitary adenomas, 289 (52.0%) were eliminated: 77 (13.9%) had an immunohistochemically confirmed prolactinoma, 119 (21.4%) patients had previous surgery, 93 (16.7%) had incomplete medical records, leaving 267 patients (48.0%) for final analysis. Of these patients, 72 (27.0%) had increased serum prolactin levels (≥23.3 ng/mL), suggestive of pituitary stalk effect (maximum prolactin level = 148.0 ng/mL). Patients with stalk effect were more likely than those with normal serum prolactin levels to present with menstrual dysfunction (29.7% vs. 19.4%; P < 0.01) and galactorrhea (11.1% vs. 2.1%; P < 0.01). Patients with lactotroph disinhibition were more likely to harbor macroadenomas than were patients who did not show lactotroph disinhibition (81.9% vs. 70.2%; P = 0.06). Among patients with increased preoperative prolactin, 77.8% experienced normalization of serum prolactin postoperatively, galactorrhea improved in 100%, sexual dysfunction resolved in 66.6%, and menstrual dysfunction among premenopausal females normalized in 73.3% at last follow-up (mean, 5.35 years; range, 0.1-10 years)., Conclusions: Transsphenoidal surgery can provide durable normalization of serum prolactin levels and related symptoms caused by pituitary stalk compression-related lactotroph disinhibition., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: 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., Methods: We performed a retrospective analysis of all patients who had surgery for a prolactinoma at our institution from January 1993 to October 2014., Results: 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., Conclusion: 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., Abbreviations: 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.

At present, pharmacological therapy of prolactinomas with dopamine agonists (DAs) is considered the treatment of choice. In most cases, giant prolactinomas respond to treatment with dopamine agonists and decrease in size during the first months of the treatment. One of the rare but dangerous complications of conservative treatment of prolactinomas with invasive growth is cerebrospinal fluid rhinorrhea., Material and Methods: 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., Results: 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., Conclusion: 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.

Prolactinomas are pituitary tumors that originate from the adenohypophysis lactotroph cells. These tumors constitute one third of all pituitary adenomas, making them the most common functional pituitary neoplasms. The signs and symptoms of patients harboring prolactin (PRL) secreting tumors may derive from hyperprolactinemia itself, as well as from direct pressure of the expanding mass on the normal pituitary gland and other surrounding tissues, in cases of invasive tumors. This review will focus on practical aspects of the medical treatment of patients with prolactinomas, and on the main differences between the treatment strategy of micro- and macroprolactinomas. Medical therapy with dopamine agonists (DA) is the preferred treatment for the vast majority of patients harboring prolactinomas. Cabergoline (CAB) is the main agent used for treating prolactinomas, achieving normoprolactinemia in 80-100% of patients with microprolactinomas, and in 75-95% of those with macroprolactinomas. Second line therapies include surgery and radiation therapy, and are indicated only in rare cases, such as patients intolerant to, or with contraindication for DAs, or patients harboring malignant or DA resistant tumors. The management principles of pregnant women with prolactinomas and of patients with suspected malignant prolactinoma are distinct from other patient populations, and are discussed separately in our review.

Microprolactinomas are the most common pituitary adenomas. In symptomatic patients, dopamine agonists are the first-line treatment of choice; when cabergoline is used, biochemical control rates between 85 and 93% have been reported. Long-term treatment is needed in most of the cases with compliance, patient convenience, and potential adverse effects representing areas requiring attention. Based on the literature published in the past 15 years, transsphenoidal surgery can lead to normal prolactin in the postoperative period in usually 71-100% of the cases with very low postoperative complication rates. Surgical expertise is the major determinant of the outcomes, and it may be a cost-effective option in young patients with life expectancy greater than 10 years (provided it is performed by experienced surgeons at high volume centers with confirmed optimal outcomes). Larger series of patients with adequate follow-up could further validate the place of transsphenoidal surgery (particularly through the endoscopic approach for which long-term results are currently limited) in the management algorithm of patients with microprolactinoma., (© 2016 European Society of Endocrinology.)

Objective To analyze the predictive factor of surgical efficacy in male patients with prolactinoma. Method The clinical data of 184 male patients with prolactinoma who had undergone surgery were retrospectively analyzed.Results Before the surgery,the serum prolactin level from 150 to 204 952 ng/ml,the tumors sized 6 to 70 mm. Macroadenoma was seen in 152 cases (82.6%) and suprasellar adenoma with visual deficitsin 75 cases (40.7%). Complete resection was achieved in 149 patients. After surgical therapy,postoperative immediate prolactin level declined in 182 patients (98.4%);57 patients (31.0%)achieved initial remission,while the disease recurred in 26 patients (45.6%).Larger tumor had significantly lower rate of complete resection (P<0.05). The recurrence rate was significantly higher in the group with higher Ki-67 index (P<0.001). The recurrence rate was significantly lower in patients with intrasellar adenoma (P<0.001).No significant relationship was found between preoperative prolactin level and complete resection (P=0.306). Conclusions Tumor size can predictthe degree of surgical resection. The prognostic factors include tumor size,preoperative growth pattern of prolactinoma,and Ki-67 index.

Objective: To summarize the treatment outcome of surgery for male prolactinoma., Methods: One hundred and eighty-four cases of male prolactinoma who underwent surgery were analyzed retrospectively.The average age of patients was 36.3 years, and the mean course was 41.9 months.The main clinical manifestation included sexual dysfunction (47.4%), headache (55.9%) and visual disturbance (46.7%). The serum prolactin levels ranged from 6.83 to 9 325.32 nmol/L.The size of tumors varied from 6 mm to 70 mm.Suprasellar adenoma with visual deficits accounted for 40.7%. 98.9% patients underwent pituitary adenoma resection via single nasal transsphenoidal approach., Results: Postoperative pathological Ki-67 index of most patients (45.1%) were less than 1%.After surgical therapy, 163 patients (88.6%) got relief of symptoms, 57 patients (31.0%) achieved initial remission, and 26 patients (45.6%) unfortunately recurred. The possibility of gross resection decreased as tumor size increased (P<0.05). Preoperative PRL had no significant relation with both tumor size and extent of resection (P>0.05). The favorable prognosis predictive factors included microadenoma, intrasellar adenoma and Ki-67 index≤3 (P<0.01)., Conclusion: Male prolactinomas is an invasive tumor with higher serum prolactin level.Tumor size could predict degree of gross resection while predictors for recurrence include tumor size, growth pattern and Ki-67 index.

Background: We report herein a retrospective analysis of the results of 142 consecutive prolactinoma cases operated upon using an endoscopic endonasal trans-sphenoidal approach over a period of 6 years., Methods: Medical records of 142 cases were analysed with respect to indications for surgery, duration of hospital stay, early remission rates, failures and recurrence rates during a median follow-up of 36 months., Results: On the basis of magnetic resonance imaging (MRI) data, 19 patients (13.4 %) had microadenoma, 113 (79.6 %) had macroadenoma, and the remaining 10 (7.0 %) had giant adenomas. Cavernous sinus invasion was identified in 25 patients by MRI and confirmed during surgery. Atypical adenoma was diagnosed in 16 patients. Sparsely granulated prolactin adenoma was identified in 99 patients (69.7 %). Our results demonstrate that male sex and higher preoperative prolactin levels are independent factors predicting persistent disease. The post-surgical complications are as follows: 2.8 % patients had meningitis, 2.1 % patients had postoperative cerebrospinal fluid leak and 2.1 % patients had panhypopituitarism. At the end of follow-up, 74.6 % patients went into remission. During follow-up period, five patients who had initial remission developed recurrence., Conclusions: Our series together with literature data suggest that an endoscopic endonasal trans-sphenoidal approach in the treatment of proloctinomas has a favourable rate of remission. According to the findings of this study, endoscopic endonasal trans-sphenoidal surgery might be an appropriate therapy choice for patients with prolactinoma who could not have been managed with recommended therapeutic modalities.

Background: Although prolactinomas are treated effectively with dopamine agonists, some have proposed curative surgical resection for select cases of microprolactinomas to avoid life-long medical therapy. We performed a cost-effectiveness analysis comparing transsphenoidal surgery (either microsurgical or endoscopic) and medical therapy (either bromocriptine or cabergoline) with decision analysis modeling., Methods: A 2-armed decision tree was created with TreeAge Pro Suite 2012 to compare upfront transsphenoidal surgery versus medical therapy. The economic perspective was that of the health care third-party payer. On the basis of a literature review, we assigned plausible distributions for costs and utilities to each potential outcome, taking into account medical and surgical costs and complications. Base-case analysis, sensitivity analysis, and Monte Carlo simulations were performed to determine the cost-effectiveness of each strategy at 5-year and 10-year time horizons., Results: In the base-case scenario, microscopic transsphenoidal surgery was the most cost-effective option at 5 years from the time of diagnosis; however, by the 10-year time horizon, endoscopic transsphenoidal surgery became the most cost-effective option. At both time horizons, medical therapy (both bromocriptine and cabergoline) were found to be more costly and less effective than transsphenoidal surgery (i.e., the medical arm was dominated by the surgical arm in this model). Two-way sensitivity analysis demonstrated that endoscopic resection would be the most cost-effective strategy if the cure rate from endoscopic surgery was greater than 90% and the complication rate was less than 1%. Monte Carlo simulation was performed for endoscopic surgery versus microscopic surgery at both time horizons. This analysis produced an incremental cost-effectiveness ratio of $80,235 per quality-adjusted life years at 5 years and $40,737 per quality-adjusted life years at 10 years, implying that with increasing time intervals, endoscopic transsphenoidal surgery is the more cost-effective treatment strategy., Conclusions: On the basis of the results of our model, transsphenoidal surgical resection of microprolactinomas, either microsurgical or endoscopic, appears to be more cost-effective than life-long medical therapy in young patients with life expectancy greater than 10 years. We caution that surgical resection for microprolactinomas be performed only in select cases by experienced pituitary surgeons at high-volume centers with high biochemical cure rates and low complication rates., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To review the incidence, spectrum of clinical manifestation, course, risk factors, as well as treatment of diabetes insipidus (DI) following neurosurgery of the pituitary gland., Methods: The files of 24 patients that underwent neurosurgery for sellar lesions, or tumor near the hypothalamus or pituitary gland at the Department of Neurosurgery, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia were retrospectively reviewed between January 2011 to December 2014. A total of 24 patients were studied, and were divided into 2 groups namely; DI and non-DI. Patient characteristics were studied using descriptive statistics. The differences in proportion between the 2 groups were found out using Z-test for proportion in 2 populations. The mean differences in the hormonal abnormalities for the 2 groups were assessed using independent t-test. All statistics are considered statistically significant when p less than 0.05., Results: During hospitalization, 13 (54.2%) out of 24 patient that underwent neurosurgery had manifestations of DI, which was transient in 5 (38.8%) and permanent in 8 (61.2%). The DI subgroup contained higher prevalence of prolactinoma, craniopharyngioma, pre-operative panhypopituitarism, and macroadenoma in MRI imaging and transphenoidal surgery. Furthermore, urine osmolality was significantly lower in the DI group post-operatively with a significant p=0.023. It was recognized that the permanent DI documented more significant numbers than other studies., Conclusion: In our study group, it was recognized that permanent DI meant that our patients needed desmopressin for more than 3 months, which documented a more significant number than other studies.

Introduction: Prolactinomas are the most common functioning pituitary adenomas. Dopamine agonists (DA) are generally very effective in treating prolactinomas by inducing tumor volume regression and endocrine remission. A minority of patients do not respond to DA or are intolerant because of side-effects. Microsurgical resection when possible is the next treatment option, but cavernous sinus, dural, or bone involvement may not allow for complete resection., Objective: We reviewed the outcome of patients with medically and surgically refractory prolactinomas treated with Gamma Knife radiosurgery (GKRS) during a 22 years follow-up period., Methods: We reviewed the patient database at the University of Virginia Gamma Knife center during a 25-year period (1989-2014), identifying 38 patients having neurosurgical, radiological and endocrine follow-up., Results: Median age at GKRS treatment was 43 years. Median follow-up was 42.3 months (range 6-207.9). 55.3 % (n = 21) were taking a dopamine agonist at time of GKRS. 63.2 % (n = 24) had cavernous sinus tumor invasion. Endocrine remission (normal serum prolactin off of a dopamine agonist) was achieved in 50 % (n = 19). GKRS induced hypopituitarism occurred in 30.3 % (n = 10). Cavernous sinus involvement was shown to be a significant negative prognosticator of endocrine remission. Taking a dopamine agonist drug at the time of GKRS showed a tendency to decrease the probability for endocrine remission., Conclusion: GKRS for refractory prolactinomas can lead to endocrine remission in many patients. Hypopituitarism is the most common side effect of GKRS.

Giant prolactinomas are rare pituitary tumours of which management can be a challenge. A 28-year-old man presented with headaches, visual impairment and behavioural changes. Clinically, the patient was found to have hypogonadism and bitemporal hemianopsia. A MRI demonstrated a pituitary tumour 76 mm in diameter and blood tests revealed a serum prolactin of 158,700 µU/mL (reference range 58-254). Initially, a craniotomy was performed. Immunohistochemistry of the tumour identified a prolactinoma with a high proliferative index and the patient was started on treatment with a dopamine agonist. A year later, neurological symptoms worsened due to regrowth of the lesion's cystic component, and so further surgery was performed. After 10 years of treatment with dopamine agonists, the prolactin levels decreased by 96.8%, there was an effective reduction in tumour size, and the neurological signs and symptoms resolved., (2015 BMJ Publishing Group Ltd.)

Background: Sellar toxoplasmosis is associated with congenital infections or immunodeficiency. The finding of Toxoplasma bradycysts in a pituitary adenoma is very unusual., Case Description: An otherwise healthy 27-year-old woman presented with secondary amenorrhea and moderately elevated prolactin levels. A macroprolactinoma was suspected on magnetic resonance imaging, and cabergoline was initiated. Although dopamine levels decreased, the tumor did not show significant shrinkage; after 2 years, transsphenoidal resection was indicated to clarify the diagnosis and to cure hyperprolactinemia. Histology showed an inactive pituitary adenoma and Toxoplasma bradycysts. Seropositivity for Toxoplasma gondii, but neither immunodeficiency nor intracerebral spread, was found. During a postoperative follow-up period of 15 months, the patient did not show any recurrence., Conclusions: Sellar toxoplasmosis in conjunction with pituitary adenoma is extremely rare. Nonfunctioning lesions should be suspected in cases of sellar masses and moderate hyperprolactinemia., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The purpose of this study was to examine the current indications for transsphenoidal surgery in the prolactinoma patient population, and to determine the outcomes of patients who undergo such operations. Transsphenoidal surgery may be indicated in prolactinoma patients who are resistant and/or intolerant to dopamine agonist (DA) therapy. We performed a retrospective review of the medical records of prolactinoma patients over a 6 year period (April 2008 to April 2014) at a large volume academic center. The median follow-up time was 12.0 months (range: 3-69). All patients who were included in the study (n=66) were treated with DA therapy and subsequently underwent an endonasal transsphenoidal operation. Of the 66 patients, 44 were women (mean age 34.2 years) and 22 were men (mean 41.7 years). There were 29 (43.9%) intolerant patients and 29 (43.9%) resistant patients. Postoperatively, 18 intolerant patients (66.7%) had normalized prolactin levels without the need for DA therapy, and five (17.2%) required DA to normalize their prolactin levels (p=0.02). Six patients (20.6%) had persistently elevated prolactin levels but were no longer receiving DA treatment (p<0.001). Postoperatively, 10 resistant patients (35.7%) had normal prolactin levels without DA therapy, and seven patients (25%) were treated with DA therapy to normalize their prolactin levels (p=0.22). Eight patients (28.6%) had supraphysiologic prolactin levels but were no longer taking a DA (p<0.001). Three patients (10.7%) were hyperprolactinemic, despite postoperative treatment with DA (p<0.001). After an appropriate treatment interval with multiple DA, radiographic follow-up, and careful clinical evaluation, prolactinoma patients can be offered surgery as an effective therapeutic option., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Epistaxis due to ruptured internal carotid artery (ICA) aneurysm embedded within a pituitary adenoma (PA) has seldom been reported in the literature. Here we want to elaborate the incidence, mechanisms, clinical manifestations, and treatment strategy for this condition. The first survived case of a patient with epistaxis and pituitary apoplexy due to ruptured aneurysm embedded within PA was reported and the literature was reviewed. A 53-year-old male patient presented to our institution with sudden onset epistaxis and progressive vision loss. Neurological examination revealed bilateral ptosis and dilated unresponsive pupils. A CT scan showed a large mass in the pituitary fossa with bony erosion. MRI revealed a large pituitary tumor and abnormal signal intensity in the tumor. No aneurysm was noted during the pre-operative MR angiography. Abundant arterial bleeding suddenly occurred during urgent transsphenoidal surgery. Digital subtraction angiography confirmed the presence of a 14 mm unexpected saccular aneurysm of right ICA in the cavernous sinus with the dome protruding into the sella turcica. Balloon test occlusion of the right ICA was undertaken and permanent occlusion was performed. The patient recovered well and received bromocriptine and thyroid hormone replacement therapy during the follow-up period. At 14-month followup, the patient had no neurological deficits, no features of ischaemia relating to the right ICA therapeutic occlusion. Our case indicated that epistaxis and pituitary apoplexy could be due to the rupture of an ICA aneurysm embedded in a PA. Clinical suspicion should remain high when evaluating any case of epistaxis and pituitary apoplexy. Optimal treatment should take into consideration individual features of the tumor, aneurysm, and patient. Making the correct diagnosis as well as identifying an appropriate management strategy is critical in the care of such patients.

The authors present an update on the various treatment modalities and discuss management strategies for prolactinomas. Prolactinomas are the most common type of functional pituitary tumor. Effective hyperprolactinemia treatment is of great importance, due to its potential deleterious effects including infertility, gonadal dysfunction and osteoporosis. Dopamine agonist therapy is the first line of treatment for prolactinomas because of its effectiveness in normalizing serum prolactin levels and shrinking tumor size. Though withdrawal of dopamine agonist treatment is safe and may be implemented following certain recommendations, recurrence of disease after cessation of the drug occurs in a substantial proportion of patients. Concerns regarding the safety of dopamine agonists have been raised, but its safety profile remains high, allowing its use during pregnancy. Surgery is typically indicated for patients who are resistant to medical therapy or intolerant of its adverse side effects, or are experiencing progressive tumor growth. Surgical resection can also be considered as a primary treatment for those with smaller focal tumors where a biochemical cure can be expected as an alternative to lifelong dopamine agonist treatment. Stereotactic radiosurgery also serves as an option for those refractory to medical and surgical therapy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The authors provide an update on the clinical manifestations and diagnostic challenges of prolactinomas. Prolactinomas are the most common pituitary adenoma seen in clinical practice. Secondary causes of hyperprolactinemia should be ruled out by assessment of the clinical history, including current medications, physical examination, pregnancy test, routine biochemical analysis with a thyroid function test, and neuroimaging, before a confirmatory diagnosis of prolactinoma is made. Prolactinomas are associated with endocrine dysfunction, affecting gonadal function and causing neurological deficits due to mass effect. The progress in elucidating the pathogenesis of prolactinomas and advances in diagnostic methods, including more sensitive diagnostic hormone assays and neuroimaging, have enriched the current diagnostic approach and management. Making the correct diagnosis is crucial to implementing the appropriate therapy. Dopamine agonist therapy remains the first line of treatment for prolactinomas, as it is effective in normalizing serum prolactin levels and reducing tumor size. Surgery is typically indicated for patients who are resistant to medical therapy or intolerant of its adverse side effects, or for those experiencing progressive neurological deficits. Nevertheless, curative surgical resection as a primary mode of treatment for smaller prolactinomas has recently gained attention as an alternative to lifelong dopamine agonist treatment., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The gram-negative bacillus Yokenella regensburgei (of the Enterobacteriaceae family) can be found in groundwater and foodstuffs, as well as the digestive tracts of insects and reptiles. Although it has been isolated from humans since its original description, it has rarely been reported as a cause of infection, and then, only in immunosuppressed patients. We report the first case of post-surgical secondary osteomyelitis due to Y. regensburgei in an immunocompetent woman who had undergone a craniotomy.

We report a 27-year-old woman with amenorrhea and galactorrhea with mildly elevated serum prolactin levels. Her MRI demonstrated a cystic macroadenoma in the left aspect of the sella and a small microadenoma in the right aspect of the sella. Endoscopic transsphenoidal resection of the tumors revealed two histologically distinct tumors. The left tumor was consistent with a silent corticotroph macroadenoma and the right tumor was a prolactin producing microadenoma. Isolated double pituitary adenomas that are clearly separated by normal pituitary gland tissue are extremely rare. The incidence is approximately 0.37-2.6%. The coexistence of double adenomas can pose diagnostic and management challenges for the pituitary neuroendocrine team., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Primary management of prolactinomas is usually medical, with surgery a secondary option where necessary. This study is a review of a single centre's experience with focused radiotherapy where benefit was not gained by medical or surgical approaches., Methods: Radiotherapy as an alternative and adjuvant treatment for prolactinomas has been performed at our institution with the linear accelerator since 1990. We present a retrospective review of 13 patients managed with stereotactic radiosurgery (SRS) and 5 managed with fractionated stereotactic radiotherapy (FSRT), as well as 5 managed with conventional radiotherapy, at the Prince of Wales Hospital. Patients with a histopathologically diagnosed prolactinoma were eligible. Those patients who had a confirmed pathological diagnosis of prolactinoma following surgical intervention, a prolactin level elevated above 500 μg/L, or a prolactin level persistently elevated above 200 μg/L with exclusion of other causes were represented in this review., Results: At the end of documented follow-up (SRS median 6 years, FSRT median 2 years), no SRS patients showed an increase in tumour volume. After FSRT, 1 patient showed an increase in size, 2 showed a decrease in size and 2 patients showed no change. Prolactin levels trended towards improvement after SRS and FSRT, but no patients achieved the remission level of <20 μg/L. Seven of 13 patients in the SRS group achieved a level of <500 μg/L, whereas no patients reached this target after FSRT., Conclusions: A reduction in prolactin level is frequent after SRS and FSRT for prolactinomas; however, true biochemical remission is uncommon. Tumour volume control in this series was excellent, but this may be related to the natural history of the disease. Morbidity and mortality after stereotactic radiation were very low in this series., (© 2014 The Royal Australian and New Zealand College of Radiologists.)

Purpose: Pediatric prolactinomas are rare, especially in children under 14 years of age. In this study, we evaluated the clinical presentation and microsurgical outcome of prolactinomas in prepubertal children., Methods: Nine patients with prolactinomas who had undergone surgical removal of the tumor before the age of 14 years were included in this retrospective study. Data on their clinical presentation, medications, physical and laboratory evaluations, radiological findings, and long-time follow-up were obtained from their medical records., Results: The main presenting symptom in the four female patients was galactorrhea (n = 4, 100%), whereas the five male patients most commonly presented with headache (n = 4, 80%) and growth retardation (n = 3, 60%). Six (66.6%) of the patients who had undergone transsphenoidal surgery were medication-free postoperatively. In three (33.3%) patients with giant adenomas, complete resection of the tumor was not achieved. One (11.1%) patient received radiotherapy after failed surgical and medical treatment. Postoperatively, electrolyte disturbances occurred in five (55.6%) patients, diabetes insipidus in two (22.2%), and thyroid dysfunction in two (22.2%). These complications resolved spontaneously. During follow-up, growth and puberty were usually normal., Conclusions: Tumor compressive symptoms and/or gonadal and growth arrest may be the primary clinical presentations of pediatric prolactinoma. Patients who are not candidates for dopamine agonist therapy are best treated surgically, based on the low mortality and high cure rates. Hypopituitarism is a rare complication and may resolve spontaneously. Following successful treatment of a prolactinoma, growth and puberty in these children are normal.

Context: A sex difference in the progression of prolactin (PRL) tumors has been disputed for years., Objective: To compare tumor characteristics and postoperative clinical course between men and women, and correlate data with estrogen receptor alpha (ERα (ESR1)) expression status., Design, Patients, and Methods: Eighty-nine patients (59 women and 30 men) operated on for a prolactinoma and followed for at least 5 years were selected. Tumors were classified into five grades according to their size, invasion, and proliferation characteristics. The ERα expression was detected by immunohistochemistry and a score (0-12) calculated as the product of the percentage of positive nuclei and the staining intensity., Results: We found a significant preponderance of high-grade tumors among men and a lower surgical cure rate in men (23%) than in women (71%). Patients resistant to medical treatment were mainly men (7/8), six of whom showed tumor progression despite postoperative medical treatment, which led to multiple therapies and eventually death in three. The median score for ERα expression was 1 in men (range, 0-8) and 8 in women (range, 0-12) (P<0.0001). The expression of ERα was inversely correlated with tumor size (r=-0.59; P<0.0001) and proliferative activity. All dopamine agonist-resistant tumors and all grade 2b (invasive and proliferative) tumors (from ten men and four women) were characterized by low ERα expression., Conclusions: PRL tumors in men are characterized by lower ERα expression, which is related to higher tumor grades, resistance to treatment, and an overall worse prognosis., (© 2015 European Society of Endocrinology.)

Background: Previous studies report impaired health-related quality of life (HRQoL) in patients with functional pituitary adenomas (FPA). We assessed HRQoL in FPA patients having undergone surgery at our University Central Hospital between 2000 and 2010, with combined adjuvant treatment given to achieve strict hormonal control., Design: A cross-sectional study including a large control population., Patients and Methods: HRQoL was assessed by the 15D in 100 FPA patients (acromegaly n = 47, Cushing's disease n = 21, prolactinoma n = 26, TSH-adenoma n = 2, gonadotropinoma n = 4), operated on a mean 7·4 (range 2·1-13·0) years earlier. An age- and gender-standardized sample of the general population (n = 4924) served as controls. HRQoL determinants were assessed by independent samples t-test and multiple regression analysis., Results: Hormonal remission rate was 90·9% and 43·9% of the patients received replacement therapy. The mean 15D scores were similar in patients and controls (0·917 vs 0·922, P = 0·568). On single dimensions, patients were worse off regarding speech and sexual activity (both P < 0·05) and better off regarding discomfort and symptoms (P < 0·05). Age (P = 0·001), co-morbidities (P = 0·009), Cushing's disease (P = 0·034), and thyroxine dose (P = 0·002) predicted impaired HRQoL, but not hypopituitarism, hydrocortisone replacement, radiotherapy, or time after surgery., Conclusions: It is possible to achieve near-normal HRQoL in surgically treated FPA patients given adjuvant treatment to achieve strict hormonal remission. However, in addition to age and co-morbidities, Cushing's disease and need for thyroxine replacement therapy predict impaired HRQoL., (© 2014 John Wiley & Sons Ltd.)

A substantial proportion of acromegalic patients have co-existent hyperprolactinaemia. To compare this group of population (AC+HPRL) to those of patients with merely hyperprolactinemia (HPRL), a retrospective analysis of patients was conducted. Data regarding clinical and immunohistochemical features, and outcome for patients were reviewed throughout the follow-up period. Four hundred and twenty-three patients were enrolled, with 329 in patients with HPRL and 94 in patients with AC+HPRL. Patients in the AC+HPRL group had a younger age at diagnosis (38.13 ± 13.31 vs. 41.95 ± 14.70 years; p=0.025) and a higher rate of invasion (p=0.007) than those in the HPRL group. The AC+HPRL group had higher GH levels but relatively lower PRL levels than the HPRL group before and after surgery. The rates of positive staining for GH and PRL in HPRL group were 15.20% and 93.01%, and the rates in AC+HPRL group were 84.04% and 87.23%. Patients with HPRL had a lower recurrence rate compared with patients in AC+HPRL group (p=0.018). Additionally, there were no significant correlations between the mean degree of preoperative GH or PRL and the positive rates of immunostaining (p>0.05, p>0.05). The Ki-67 indexes in HPRL group and AC+HPRL group were 3.07% ± 2.13 and 2.33% ± 1.71, respectively (p=0.001). In conclusion, acromegalic patients with hyperprolactinemia need careful and long-term follow-up following an operation.

To evaluate the specific characteristics in acromegalic patients with hyperprolactinemia by analyzing the differences between patients with different Ki-67 values. Between 2002 and 2010, a set of data on 61 patients undergoing transsphenoidal surgery was available at the Department of Neurosurgery, Provincial Hospital Affiliated to Shandong University. Patients were divided into Ki-67 >3% group and <3% group. A retrospective analysis of clinical, hormonal, immunohistochemical, and imaging was observed in all patients. There were no significant differences in age, gender, tumor size and apoplexy between the two groups. Time interval in Ki-67 ≥3% group was longer than <3% group (P=0.037). Patients in Ki-67 >3% group had a higher rate of invasiveness (P=0.048), higher incidences of diabetes mellitus (P=0.036), coarse facial features (P=0.048), large hands and feet (P=0.003), higher GH levels (P<0.05), higher diabetes insipidus rate (P<0.001), and more frequent recurrence (P=0.011) than Ki-67 <3% group. Patients with higher Ki-67 value harbored longer time interval, more aggressive tumors, more acromegaly manifestations, higher GH level, and higher recurrence than patients with lower Ki-67 value.

The coexistence of pituitary adenoma (PA) and anterior communicating artery aneurysm is extremely rare, making the diagnosis difficult and the treatment challenging. Herein, we present a PA patient with intracranial hemorrhage due to rupture of an anterior communicating artery aneurysm. For the best diagnosis of intracranial aneurysm among PA patients, cranial magnetic resonance together with three-dimensional time-of-flight magnetic resonance angiography are strongly recommended. Previous treatment of the intracranial aneurysm is advisable and essential to avoid possible catastrophic bleeding during the transsphenoidal or microsurgical removal of PA.

Hyperprolactinemia occurs in patients with a prolactinoma and in those with a sellar mass compressing the pituitary stalk. Distinguishing these two diagnostic possibilities guides treatment with dopamine agonist therapy or surgical resection. We aimed to identify a simple, predictive algorithm to aid in the diagnosis of prolactinoma in patients with an elevated serum prolactin and a sellar mass. A case-control analysis of pathologically confirmed prolactinomas and non-endocrine secreting controls from the University of California, San Francisco was performed. From 2001 to 2011, this resulted in 177 patients with prolactinomas and 87 controls. Univariate and classification and regression tree (CART) analysis determined the significance of demographic variables, patient symptoms, laboratory values, and radiographic findings in distinguishing pathology. Additionally, a subset of patients with mildly elevated serum prolactin (25-125 ng/ml) was independently analyzed. Prolactinomas had a mean pre-operative prolactin of 858 ng/ml versus 17.57 ng/ml in controls (p<0.01). One hundred and two (62.6%) of the prolactinomas were macroadenomas (size >10mm) compared to 74 (92.5%) of the controls (p<0.01). CART analysis identified preoperative prolactin (>41.5 ng/ml), age (<40.5 years), and size (<17 mm) as being predictive of prolactinoma with a misclassification rate of 7.9% (21/264). Similar analysis on the subset of patients with mildly elevated serum prolactin (<125 ng/ml) identified size (<2.5 cm) and pre-operative prolactin (>40 ng/ml) as key variables. These two factors correctly predicted 98.6% (69/70) of cases. Our model correctly classifies most patients with elevated serum prolactin and identifies those patients most amenable to surgical treatment., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Pituitary carcinomas, which are rare, generally present with craniospinal and systemic metastases. Although several treatments exist, the prognoses of patients with pituitary carcinomas are extremely poor to date. In this report, the authors describe the case of a 23-year-old male who had undergone trans-sphenoidal surgery and radiotherapy for an invasive prolactinoma. Seven years later, he presented with a new 4th ventricle metastasis from the pituitary lesion, and it was diagnosed with a pituitary carcinoma. He underwent resection and Gamma-knife radiosurgery (GKRS). The tumor has been well controlled for over 3 years. To our knowledge, there have been no reports of the effects of GKRS in patients with pituitary carcinomas. GKRS might have considerable effects in the treatment of pituitary carcinomas.

Medical therapy with dopaminergic agonists (DAs) has been used for several decades for the treatment of both micro- and macroprolactinomas, without much differentiation between the two conditions. While most cases respond well to DAs in terms of prolactin normalization and control of tumor growth, DAs are often needed for many years, or even for lifetime. Concerns have been raised recently about the possible side effects of long-term use of these medications on the anatomy and function of the heart valves. While macroprolactinomas are rarely surgically curable, pituitary surgery in expert hands is a safe and effective method to permanently cure microprolactinomas, with long-term cure rates around 70 %. In this article, I will review the data on safety of DAs an on the effectiveness and safety of surgery, and I will make an argument that surgery should be offered as a possible therapy to microprolactinoma patients, provided that an experienced pituitary neurosurgeon is available.

Prolactinomas account for approximately 40 % of all pituitary adenomas. Over 95 % of prolactinomas are microadenomas (< 10 mm diameter). Treatment is indicated to correct hypogonadism, restore other hormonal deficits, and alleviate local mass effects. Dopamine agonists (DA) are highly effective in achieving these goals and are well-tolerated. The vast majority of prolactinomas will respond to conventional doses of cabergoline (≤2 mg/week) that do not carry an increased risk of cardiac valvular abnormalities. DA therapy may be successful withdrawn in a subset of patients and thus is not necessarily a lifelong commitment. Although transsphenoidal surgery (TSS) is an option for prolactinoma treatment, it is less effective than medical management, carries considerably more risk, and is more expensive. The benefit/risk ratio for DA therapy compared to TSS actually becomes increasingly more favorable as tumor size increases. Therefore DA should remain the clear treatment of choice for essentially all patients with prolactinomas, reserving TSS as a second-line option for the very small number of patients that do not tolerate or are completely resistant to DA therapy.

Context: Hormone secretion by functioning pituitary tumors is characterized by increased basal (nonpulsatile) secretion, enhanced pulse frequency, amplified pulse mass, and increased disorderliness., Objective: The objective of the study was to quantify (subtle) abnormalities of hormone secretion by pituitary adenomas and the influence of selective pituitary surgery and suppressive medications on these parameters., Methods: Approximate entropy (ApEn) was quantified with a refined algorithm, spikiness by a new method to evaluate sudden short-lived increases in hormone levels, and pulsing regularity, determined with a fully automated deconvolution program. These 3 distinct measures of secretory disruption were compared in untreated and treated patients with acromegaly, prolactinoma, and Cushing's disease together with matching profiles in healthy controls., Results: ApEn and spikiness were markedly increased in all untreated patient groups and normalized after pituitary surgery in acromegaly and hypercortisolism. In contrast, hormone-suppressive medical treatment in acromegaly and prolactinoma did not normalize ApEn. Spikiness normalized in acromegalic patients but not in prolactinoma. GH and cortisol pulsing regularity was elevated in acromegaly and Cushing's disease, respectively, and normalized after surgery. Medical treatment caused normalization of pulsing regularity in acromegaly but not in prolactinoma patients., Conclusion: This study extends the understanding of disorganized hormone secretion by hyperfunctioning pituitary adenomas. The new findings are increased spikiness in all 3 tumor groups and increased pulsing regularity in GH- and ACTH-secreting adenomas. The mechanisms behind the marked pattern irregularity and the selective normalization by surgical and medical therapies are not established yet but may include diminished feedback signaling in addition to the anatomical and functional disorganization of intrapituitary cell networks.