Nonalcoholic Fatty Liver Disease, Bone and Muscle Quality in Prolactinoma: A Pilot Study.

OBJECTIVE: Hyperprolactinemia has negative impacts on metabolism and musculoskeletal health. In this study, individuals with active prolactinoma were evaluated for nonalcoholic fatty liver disease (NAFLD) and musculoskeletal health, which are underemphasized in the literature. METHODS: Twelve active prolactinoma patients and twelve healthy controls matched by age, gender, and BMI were included. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was used to evaluate hepatic steatosis and magnetic resonance elastography (MRE) to evaluate liver stiffness measurement (LSM). Abdominal muscle mass, and vertebral MRI-PDFF was also evaluated with MRI. Body compositions were evaluated by dual energy X-ray absorptiometry (DXA). The skeletal muscle quality (SMQ) was classified as normal, low and weak by using "handgrip strength/appendicular skeletal muscle mass (HGS/ASM)" ratio based on the cut-off values previously stated in the literature. RESULTS: Prolactin, HbA1c and CRP levels were higher in prolactinoma patients (p<0.001, p=0.033 and p=0.035, respectively). The median MRI-PDFF and MRE-LSM were 3.0% (2.01-15.20) and 2.22 kPa (2.0-2.5) in the prolactinoma group and 2.5% (1.65-10.00) and 2.19 kPa (1.92-2.54) in the control group, respectively and similiar between groups. In prolactinoma patients, liver MRI-PDFF showed a positive and strong correlation with the duration of disease and traditional risk factors for NAFLD. Total, vertebral and pelvic bone mineral density was similar between groups, while vertebral MRI-PDFF tended to be higher in prolactinoma patients (p=0.075). Muscle mass and strength parameters were similar between groups, but HGS/ASM tended to be higher in prolactinoma patients (p=0.057). Muscle mass was low in 33.3% of prolactinoma patients and 66.6 of controls. According to SMQ, all prolactinoma patients had normal SMQ, whereas 66.6% of the controls had normal SMQ. CONCLUSION: Prolactinoma patients demonstrated similar liver MRI-PDFF and MRE-LSM to controls despite their impaired metabolic profile and lower gonadal hormone levels. Hyperprolactinemia may improve muscle quality in prolactinoma patients despite hypogonadism.

Invasive Giant Prolactinoma.

A 64-year-old man presented with an 8-year history of decreased libido, impotence, and blurred vision. The neurologic examination revealed a mild left facial weakness, visual acuity of (20/60), and right homonymous hemianopia. Laboratory investigation of serum prolactin was 7896 ng/mL. Testosterone, free T4, and adrenocorticotropic hormone were all decreased. Brain magnetic resonance imaging showed a giant sellar/suprasellar lesion, compressing on the brainstem and extending to the cerebellopontine angle. A diagnosis of panhypopituitarism secondary to a giant macroprolactinoma was made. The patient was started on hormonal replacement therapy and underwent craniotomy and tumor resection. The histopathologic findings were compatible with prolactinoma. Invasive giant prolactinomas are defined as 1) tumor size of >4 cm in diameter; 2) serum prolactin of >1000 ng/mL; and 3) mass effect or hyperprolactinemia-induced symptomatology. The management of invasive giant prolactinoma commonly comprises a multimodal approach of both medical treatment and surgical intervention.

A giant invasive macroprolactinoma with recurrent nasal bleeding as the first clinical presentation: case report and review of literature.

BACKGROUND: Giant prolactinoma (> 4 cm in dimension) is a rare disorder. Invasive macroprolactinoma has the potential to cause base of skull erosion and extend into the nasal cavity or even the sphenoid sinus. Nasal bleeding caused by intranasal tumor extension is a rare complication associated with invasive giant prolactinoma. We report a case of giant invasive macroprolactinoma with repeated nasal bleeding as the initial symptom. CASE PRESENTATION: A 24-year-old man with an invasive giant prolactinoma in the nasal cavity and sellar region who presented with nasal bleeding as the initial symptom, misdiagnosed as olfactory neuroblastoma. However, markedly elevated serum prolactin levels (4700 ng/mL), and a 7.8-cm invasive sellar mass confirmed the diagnosis of invasive giant prolactinoma. He was treated with oral bromocriptine. Serum prolactin was reduced to near normal after 6 months of treatment. Follow-up magnetic resonance imaging showed that the sellar lesion had disappeared completely and the skull base lesions were reduced. CONCLUSION: This case is notable in demonstrating the aggressive nature of untreated invasive giant prolactinomas which can cause a diagnostic difficulty with potential serious consequences. Early detection of hormonal levels can avoid unnecessary nasal biopsy. Early identification of pituitary adenoma with nasal bleeding as the first symptom is particularly important.

DRD2 expression based on 18F-fallypride PET/MR predicts the dopamine agonist resistance of prolactinomas: a pilot study.

PURPOSE: The dopamine agonists (DA) have been used widely to treat prolactinomas. However, it is difficult to predict whether the patient will be responsive to DA treatment. METHODS: We aimed to investigate whether the in vivo expression of DRD2 based on 18F-fallypride PET/MR could predict the therapeutic effect of DA on prolactinomas. Seven patients with prolactinomas completed 18F-fallypride PET/MR. Among them, three patients underwent surgery and further tumor immunohistochemistry. Imaging findings and immunohistochemical staining were compared with treatment outcomes. RESULTS: 18F-fallypride PET/MR was visually positive in 7 of 7 patients, and DRD2 target specificity could be confirmed by immunohistochemical staining. A significantly lower tracer standard uptake value (SUV) could be detected in the resistant patients (n = 3) than in the sensitive patients (n = 4; SUVmean, 4.67 ± 1.32 vs. 13.57 ± 2.42, p < 0.05). DRD2 expression determined by 18F-fallypride PET/MR corresponded with the DA treatment response. CONCLUSION: 18F-fallypride PET/MR may be a promising technique for predicting DA response in patients with prolactinoma.

Prolactinoma extension as a contributing factor in dopamine agonist-induced CSF rhinorrhea: a systematic review of the literature.

BACKGROUND: Dopamine agonist-induced cerebrospinal fluid (CSF) rhinorrhea is an uncommon treatment-related complication arising in 6.1% of prolactinoma patients treated with dopamine agonists. Locally invasive prolactinomas may create CSF fistulae through formation of dural and osseous skull base defects. Tumor shrinkage secondary to dopamine agonist therapy unmasks skull base defects, thus inducing CSF rhinorrhea. In these cases, repair of the leak may be achieved through collaborative surgical intervention by rhinologists and neurosurgeons. Multiple variables have been investigated as potential contributors to the risk of CSF rhinorrhea development in medically treated prolactinoma patients, with little consensus. OBJECTIVE: The primary aim of our study was the characterization of risk factors for CSF rhinorrhea development following dopamine agonist treatment. METHODS: A systematic review of the literature was conducted to identify cases of CSF rhinorrhea following dopamine agonist treatment of prolactinoma. The clinical history, radiographic findings and treatment outcomes are discussed. RESULTS: Fifty-four patients with dopamine agonist-induced CSF rhinorrhea were identified across 23 articles published from 1979 to 2019. Description of diagnostic imaging [computed tomography (CT)/magnetic resonance imaging (MRI)] was not provided for 18/54 subjects. For the 36 cases that described prolactinoma appearance on CT or MRI, invasion of the cavernous sinuses was reported in 13 (36.1%) and invasion of the sphenoid sinus was reported in 18 (50%). CONCLUSION: Based on our systematic review, we propose that CT findings of osseous erosion of the sella or the anterior skull base may predict dopamine agonist-induced CSF rhinorrhea. We recommend obtaining a thin-slice CT of the sinuses in cases with MRI evidence of sphenoid involvement.

Endoscopic Transnasal Approach for Microprolactinomas with Experience of 105 Cases in a Single Center: Paradigmal Shift for Conventional Medical Therapy.

OBJECTIVE: The classically recommended first-line therapy for microprolactinomas is medical therapy. In the presence of drug resistance and intolerance after the use of dopamine agonists or when the patients prefer surgery instead of medication, surgical treatment is considered as second-line treatment. The high hormonal remission and low complication rates after surgery for microprolactinomas suggest that the surgical outcome of endoscopic surgeries may be better than medical therapy in well-selected patients. This study reports a large series of patients with microprolactinoma treated by endoscopic transnasal approach and evaluates the efficiency of surgical treatment. METHODS: Our study is a retrospective cohort analysis of patients with microprolactinoma operated on by an endoscopic transnasal approach between August 1997 and February 2022 by an experienced pituitary surgeon in a single tertiary center. Inclusion criteria for microprolactinoma were based on increased prolactin levels, microadenoma (<10 mm in diameter) on pituitary magnetic resonance imaging, and histopathologically verified lactotroph adenoma. RESULTS: The mean follow-up was 74.90 months (range, 6-207). The postoperative day 1 remission rate was 85.7% and the long-term remission rate was 74.3%. The long-term remission rates of the patients in the preference group were significantly higher than those of the patients in the resistant or intolerance group (P = 0.002). Patients who used dopamine agonists for more than 3 years had a lower remission rate compared with patients who used dopamine agonists for a shorter period or who did not use it (P = 0.01). The surgical complication rate was 4.76%. CONCLUSIONS: According to our findings, endoscopic transnasal surgery performed by an experienced neurosurgeon in well-selected patients with microprolactinoma can be offered with cure rates superior to medical therapy and may be an alternative first-line treatment option to dopamine agonists.

Surgical Technique and Efficacy Analysis of Extra-pseudocapsular Transnasal Transsphenoidal Surgery for Pituitary Microprolactinoma.

OBJECTIVE: To elucidate the role of transsphenoidal surgery in the treatment of pituitary microprolactinoma. METHODS: The clinical data of 107 prolactinoma cases treated by extra-pseudocapsular transnasal transsphenoidal surgery (ETTS) for different indications in our department since 2011 was retrospectively analyzed. RESULTS: The most common indication was the ineffectiveness of oral medication (41.1%), followed by the personal willingness of the patient (35.5%), and 20.6% of the patients were young women with clear tumor boundaries. The pseudocapsule was not observed in 63 cases (58.9%), incomplete pseudocapsule was observed in 26 cases (24.3%), and complete pseudocapsule in 18 cases (16.8%). A total of 97 patients (90.7%) obtained 1-year post-operation remission. According to the relative location of the adenoma and pituitary gland on the MRI scan, 46 patients were classified into a central type, 59 a lateral type, and 2 a supra-pituitary type. Two patients developed hypogonadism, one patient developed hypocortisolism, and one patient developed post-operative hypothyroidism. Two patients were administrated with hormone replacement treatment, and the treatment was stopped within one week. There was no permanent hypopituitarism. Further investigation demonstrated that the adenoma types could affect the remission rates of hyperprolactinemia and gross total resection rate in microprolactinoma. CONCLUSION: ETTS was an effective treatment for pituitary microprolactinomas. This could be the first choice for patients who presented enclosed adenoma on the MRI and were potentially curable in a preoperative evaluation. Maximal safe removal of the adenoma by ETTS with the aim to increase the sensitivity of the drugs was also recommended for patients with invasive dopamine agonist resistant prolactinomas and patients with difficulty in childbirth.

Prolactinoma - which patients react favorably to cabergoline medication?

Objective. Prolactinoma, as a common endocrine disorder and the most frequent type of pituitary tumor, acts primarily as a suppressor on the gonadal functions. It is generally successfully treated with dopamine agonists; however, treatment resistance still remains in an unneglectable ratio. In this study, we aimed to identify factors, which may play a role in the treatment response. Methods. Seventy-six patients with prolactinoma, who have been routinely followed between 2018 and 2022 in Istanbul Research and Educational Hospital Endocrinology Outpatient Clinic, were included into the study. Initial prolactin level, adenoma size, baseline weight, body mass index (BMI), glucose, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels were obtained from the patient's medical records. The patients were divided into two groups: treatment respondent and non-respondent (refractory) ones, according to treatment response in the duration as suggested by the guidelines. The treatment respondent and non-respondent groups were compared according to the initial and the 3rd month prolactin levels, adenoma size, weight, BMI, and metabolic values. Results. The initial tumor diameter was 15.27±10.62 mm in the refractory and 7.42±4.42 mm in the treatment respondent groups (p=0.01). The refractory group had higher prolactin baseline level 269.96±275.78 µg/l vs. 124.55±67.35 µg/l of the respondent group (p=0.01). The refractory group had higher the 3rd month prolactin level 50.97±52.55 µg/l vs. 29.70±27.31 µg/l of the respondent group (p=0.04). The refractory group had higher frequency of cystic/hemorrhagic adenoma (47.6%, n=11/21) (p=0.01), baseline pituitary failure (33.3%, n=7/21) (p=0.01), and baseline cavernous sinus invasion (25.8, n=5/21) (p=0.01). The treatment respondent group had lower initial body weight (69.54±17.51 kg vs. 83.29±16.21 kg) (p<0.01), and lower BMI (25.98±5.47 kg/m2 vs. 27.69±6.42 kg/m2) (p=0.02). Conclusions. In this study, initial tumor size, male gender, weight, BMI, the 3rd month prolactin level, initial pituitary deficiency, and cystic/hemorrhagic component in pituitary imaging in patients with prolactinoma were associated with a lower treatment response.

Optical coherence tomography angiography characteristics of the retinal and optic disc morphology in prolactinoma.

PURPOSE: To investigate changes in the retinal and optic disc (OD) morphology in prolactinoma patients without optical chiasmal compression and/or visual field defects using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional imaging study, 16 consecutive prolactinoma patients (group 1, 32 eyes) and 15 age- and gender-matched healthy subjects (group 2, 30 eyes) underwent a thorough neuro-ophthalmological examination, which included testing for the presence of any intracranial compressive lesion that could cause optic neuropathy. Retinal morphological parameters, outer retinal and choriocapillaris flow areas, as well as OD vessel density (VD) and retinal nerve fiber layer (RNFL) thickness in for quadrants were then measured using OCTA. RESULTS: Mean age (p = 0.537) and gender (p = 0.385) of participants in groups 1 and 2 did not differ significantly. The mean BCVA for both groups was 0.00 ± 0.00 logMAR. Microadenomas made up the majority of prolactinomas (87.1 %). All retinal morphological parameters in deep capillary plexus (excluding foveal VD) differed significantly between groups 1 and 2 (whole: p < 0.001, parafoveal: p = 0.021, and perifoveal: p < 0.001). Peripapillary RNFL thickness in temporal (p < 0.001), nasal (p = 0.010), and inferior (p = 0.007) quadrants also differed significantly between the two groups. Foveal deep (r = -0.304, p = 0.035) and choriocapillaris flow (r = -0.511, p = 0.008) were negatively correlated with tumor size at diagnosis. CONCLUSIONS: Significant microvascular morphological changes, particularly in the deep retinal layer, as well as in the peripapillary RNFL thickness, were observed in prolactinoma patients. OCTA appears to be capable of detecting non-manifest circumpapillary and even intra-retinal microvascular changes even when there are no obvious signs of prolactinoma-related ocular complications caused by chiasmal compression.

Implementation of functional imaging using 11C-methionine PET-CT co-registered with MRI for advanced surgical planning and decision making in prolactinoma surgery.

PURPOSE: To report the first experience of our multidisciplinary team with functional imaging using 11C-methionine positron emission tomography-computed tomography (11C-methionine PET-CT) co-registered with MRI (Met-PET/MRICR) in clinical decision making and surgical planning of patients with difficult to treat prolactinoma. METHODS: In eighteen patients with prolactinoma, referred to our tertiary referral centre because of intolerance or resistance for dopamine agonists (DA), Met-PET/MRICR was used to aid decision-making regarding therapy. RESULTS: Met-PET/MRICR was positive in 94% of the patients. MRI and Met-PET/MRICR findings were completely concordant in five patients, partially concordant in nine patients, and non-concordant in four patients. In five patients Met-PET/MRICR identified lesion(s) that were retrospectively also visible on MRI. Met-PET/MRICR was false negative in one patient, with a cystic adenoma on conventional MRI. Thirteen patients underwent transsphenoidal surgery, with nine achieving full biochemical remission, two clinical improvement and near normalized prolactin levels, and one patient clinical improvement with significant tumour reduction. Hence, nearly all patients (94%) were considered to have a positive outcome. Permanent complication rate was low. Three patients continued DA, two patients have a wait and scan policy. CONCLUSION: Met-PET/MRICR can provide additional information to guide multidisciplinary preoperative and intraoperative decision making in selected cases of prolactinoma. This approach resulted in a high remission rate with a low rate of complications in our expert centre.

11C-methionine PET aids localization of microprolactinomas in patients with intolerance or resistance to dopamine agonist therapy.

PURPOSE: To assess the potential for 11C-methionine PET (Met-PET) coregistered with volumetric magnetic resonance imaging (Met-PET/MRCR) to inform clinical decision making in patients with poorly visualized or occult microprolactinomas and dopamine agonist intolerance or resistance. PATIENTS AND METHODS: Thirteen patients with pituitary microprolactinomas, and who were intolerant (n = 11) or resistant (n = 2) to dopamine agonist therapy, were referred to our specialist pituitary centre for Met-PET/MRCR between 2016 and 2020. All patients had persistent hyperprolactinemia and were being considered for surgical intervention, but standard clinical MRI had shown either no visible adenoma or equivocal appearances. RESULTS: In all 13 patients Met-PET/MRCR demonstrated a single focus of avid tracer uptake. This was localized either to the right or left side of the sella in 12 subjects. In one patient, who had previously undergone surgery for a left-sided adenoma, recurrent tumor was unexpectedly identified in the left cavernous sinus. Five patients underwent endoscopic transsphenoidal selective adenomectomy, with subsequent complete remission of hyperprolactinaemia and normalization of other pituitary function; three patients are awaiting surgery. In the patient with inoperable cavernous sinus disease PET-guided stereotactic radiosurgery (SRS) was performed with subsequent near-normalization of serum prolactin. Two patients elected for a further trial of medical therapy, while two declined surgery or radiotherapy and chose to remain off medical treatment. CONCLUSIONS: In patients with dopamine agonist intolerance or resistance, and indeterminate pituitary MRI, molecular (functional) imaging with Met-PET/MRCR can allow precise localization of a microprolactinoma to facilitate selective surgical adenomectomy or SRS.

Aggressive giant prolactinoma: a case report.

BACKGROUND: Managing treatment-resistant aggressive giant prolactinoma can be challenging, as the diagnosis is often complex, and treatment beyond dopamine agonists, surgery, and radiotherapy is limited. CASE PRESENTATION: A 21-year-old Malay woman first presented to our hospital at the age of 16 years with 1-year history of reduced vision and 2 years of amenorrhea. Her baseline prolactin level was 255,894 µIU/mL with secondary hypogonadism, and pituitary magnetic resonance imaging revealed a giant prolactinoma (2.8 × 3.2 × 4.2 cm3) with suprasellar extension and optic chiasmal compression. She was initially treated with cabergoline, and reductions in the prolactin level and tumor mass were achieved, leading to vision improvement and resumption of normal menstruation. However, she developed recurrent tumor growth and hyperprolactinemia, causing relapse of symptoms, and she needed surgery. Eventually, despite three tumor debulking surgeries and escalation of cabergoline doses up to 1 mg/day, her tumor progressed with aggressive characteristics. Following a multidisciplinary meeting, the patient is initiated on temozolomide therapy after considering the long-term side effects of radiotherapy in her case. CONCLUSION: This case highlights the importance of early identification of treatment-resistant prolactinoma and the need for a multidisciplinary approach in managing aggressive prolactinoma in young patients, particularly regarding timely implementation of temozolomide therapy.

Bone microarchitecture impairment in prolactinoma patients assessed by HR-pQCT.

PURPOSE: Prolactinoma may reduce bone mineral density (BMD) and increase fracture risk, but its influence on bone microarchitecture remains to be elucidated. The purpose of this study is to evaluate bone microarchitecture parameters by high-resolution peripheral quantitative computed tomography (HR-pQCT) in prolactinoma patients. METHODS: 31 prolactinoma patients and 62 age- and sex-matched healthy controls in our center were included, and HR-pQCT was used to evaluate their bone microarchitecture at the radius and tibia. Z-scores for bone microarchitecture parameters were calculated based on previously published reference. RESULTS: After adjusting for height and weight, prolactinoma patients had lower trabecular (- 0.011 mm, p = 0.005) and cortical thickness (- 0.116 mm, p = 0.008) and cortical area (- 6.0 mm2, p = 0.013) at radius, as well as lower trabecular (- 0.014 mm, p = 0.008) and cortical (- 0.122 mm, p = 0.022) thickness at tibia compared with the controls. Patients with higher prolactin level had more severe bone microarchitecture impairments. After adjusting for prolactin level and age, male patients had lower trabecular volumetric BMD (vBMD), trabecular number, trabecular thickness, and cortical porosity at radius, as well as lower trabecular vBMD, trabecular bone volume fraction, trabecular number, and cortical area, and higher trabecular separation at tibia compared with female patients. Z-score for radius vBMD was correlated with Z-score for areal BMD (aBMD) at lumbar and femoral neck, while Z-score for tibia vBMD was correlated with Z-score for lumbar aBMD, and some patients with vBMD Z-score below - 2.0 had aBMD Z-score within normal range. CONCLUSION: Peripheral bone microarchitecture was impaired in prolactinoma patients, especially in patients with higher prolactin level. We compared the bone microarchitecture of prolactinoma patients and healthy controls by high-resolution peripheral quantitative computed tomography (HR-pQCT), and found that many bone microarchitecture parameters were impaired among prolactinoma patients. Such impairment was more prominent among patients with higher prolactin level.

Is there an increased cardiovascular risk in patients with prolactinoma? A challenging question.

PURPOSE: Epicardial adipose tissue thickness (EATT) is considered to be a surrogate for visceral fat and a novel cardiovascular risk indicator. Hyperprolactinemia has been shown to be associated with increased cardiovascular risk. The aim was to evaluate the association between EATT, carotid intima media thickness (CIMT), and cardiac functions in patients with prolactinoma. METHODS: Patients with the diagnosis of prolactinoma were included. The control group consisted of healthy age matched individuals with normal prolactin levels. Prolactin, fasting blood glucose (FBG), insulin, hemoglobin A1c (HbA1c), alanine aminotransferase (ALT), total cholesterol, triglycerides, and high (HDL) and low density lipoprotein (LDL) cholesterol were measured. EATT, CIMT, cardiac systolic, and diastolic functions were determined using echocardiography. RESULTS: We evaluated 67 patients with prolactinoma (aged 40.7 ± 11.9 years, F/M: 51/16) and 57 controls (aged 42.5 ± 7.4 years, F/M: 36/21). Of the 67 patients, 24 had normal prolactin levels. FBG level was higher in prolactinoma patients than in controls. Patients and controls had similar HbA1c, HOMA-IR, ALT, total, HDL, LDL cholesterol, and triglycerides levels, and similar cardiac systolic and diastolic functions. Prolactinoma patients had greater EATT (3.0 ± 0.5 mm vs. 2.6 ± 0.4 mm, p < 0.001) and CIMT (0.57 ± 0.08 mm vs. 0.52 ± 0.04 mm, p = 0.03) than controls. EATT was correlated with body mass index, FBG, HbA1c, and triglyceride levels. CONCLUSIONS: EATT and CIMT were greater in patients with prolactinoma, although they had normal cardiac systolic and diastolic functions.

Tumor volume improves preoperative differentiation of prolactinomas and nonfunctioning pituitary adenomas.

PURPOSE: Both prolactinomas and nonfunctioning adenomas (NFAs) can present with hyperprolactinemia. Distinguishing them is critical because prolactinomas are effectively managed with dopamine agonists, whereas compressive NFAs are treated surgically. Current guidelines rely only on serum prolactin (PRL) levels, which are neither sensitive nor specific enough. Recent studies suggest that accounting for tumor volume may improve diagnosis. The objective of this study is to investigate the diagnostic utility of PRL, tumor volume, and imaging features in differentiating prolactinoma and NFA. METHODS: Adult patients with pathologically confirmed prolactinoma (n = 21) or NFA with hyperprolactinemia (n = 58) between 2013 and 2020 were retrospectively identified. Diagnostic performance of clinical and imaging variables was analyzed using receiver-operating characteristic curves to calculate area under the curve (AUC). RESULTS: Tumor volume and PRL positively correlated for prolactinoma (r = 0.4839, p = 0.0263) but not for NFA (r = 0.0421, p = 0.7536). PRL distinguished prolactinomas from NFAs with an AUC of 0.8892 (p < 0.0001) and optimal cut-off value of 62.45 ng/ml, yielding a sensitivity of 85.71% and specificity of 94.83%. The ratio of PRL to tumor volume had an AUC of 0.9647 (p < 0.0001) and optimal cut-off value of 21.62 (ng/ml)/cm3 with sensitivity of 100% and specificity of 82.76%. Binary logistic regression found that PRL was a significant positive predictor of prolactinoma diagnosis, whereas tumor volume, presence of cavernous sinus invasion, and T2 hyperintensity were significant negative predictors. The regression model had an AUC of 0.9915 (p < 0.0001). CONCLUSIONS: Consideration of tumor volume improves differentiation between prolactinomas and NFAs, which in turn leads to effective management.

Identification of an optimal prolactin threshold to determine prolactinoma size using receiver operating characteristic analysis.

Prolactinomas represent the most common type of secretory pituitary neoplasms, with a therapeutic management that varies considerably based on tumour size and degree of hyperprolactinemia. The aim of the current study was to evaluate the relationship between serum prolactin (PRL) concentrations and prolactinoma size, and to determine a cut-off PRL value that could differentiate micro- from macro-prolactinomas. A retrospective cohort study of 114 patients diagnosed with prolactinomas between 2007 and 2017 was conducted. All patients underwent gadolinium enhanced pituitary MRI and receiver operating characteristic (ROC) analyses were performed. 51.8% of patients in this study were men, with a mean age at the time of diagnosis of 42.32 ± 15.04 years. 48.2% of the total cohort were found to have microadenomas. Baseline serum PRL concentrations were strongly correlated to tumour dimension (r = 0.750, p = 0.001). When performing the ROC curve analysis, the area under the curve was 0.976, indicating an excellent accuracy of the diagnostic method. For a value of 204 µg/L (4338 mU/L), sensitivity and specificity were calculated at 0.932 and 0.891, respectively. When a cut off value of 204 µg/L (4338 mU/L) was used, specificity was 93.2%, and sensitivity 89.1%, acceptable to reliably differentiate between micro- and macro- adenomas.

Gamma knife radiosurgery for high-risk lactotroph adenomas: Long-term results.

Gamma Knife radiosurgery (GKRS) for lactotroph adenomas (LAs) or prolactinomas is limited due to the effectiveness of medical treatments and surgery. Cases who are refractory to medical treatment and/or surgery may be managed with GKRS. We aimed to describe the effectiveness of GKRS for high-risk lactotroph adenomas (HRLAs) and LAs that were medically and surgically refractory. We analyzed our series of patients with HRLAs and LAs who were managed with GKRS following failed medical treatment and surgery and who had at least three years of follow-up. A total of 52 patients (22 HRLAs and 30 LAs) were included in the analysis of radiological, endocrine, and clinical outcomes. Radiological control was achieved in 68.2% of subjects in the HRLA group and 96.7% of subjects in the LA group. Hormonal control was achieved in 68.2% of patients in the HRLA group and 80% of patients in the LA group. On univariate analysis, hormonal control was significantly associated with pre-treatment volume (p = 0.007), higher margin dose (p = 0.002) and Ki-67 proliferative index (p = 0.007). Complications involved new pituitary hormone deficiencies in 19.2% of patients and asymptomatic peripheral visual field defect in 1.9% of patients. To the best of our knowledge, this is the first study to examine the effectiveness of GKRS in LAs and HRLAs, with the highest median follow-up in the literature. High hormonal control rate, even in HRLAs, and lower complication rates suggest that GKRS should be part of the techniques for managing treatment refractory LAs.

Radiomics With Ensemble Machine Learning Predicts Dopamine Agonist Response in Patients With Prolactinoma.

CONTEXT: Early identification of the response of prolactinoma patients to dopamine agonists (DA) is crucial in treatment planning. OBJECTIVE: To develop a radiomics model using an ensemble machine learning classifier with conventional magnetic resonance images (MRIs) to predict the DA response in prolactinoma patients. DESIGN: Retrospective study. SETTING: Severance Hospital, Seoul, Korea. PATIENTS: A total of 177 prolactinoma patients who underwent baseline MRI (109 DA responders and 68 DA nonresponders) were allocated to the training (n = 141) and test (n = 36) sets. Radiomic features (n = 107) were extracted from coronal T2-weighed MRIs. After feature selection, single models (random forest, light gradient boosting machine, extra-trees, quadratic discrimination analysis, and linear discrimination analysis) with oversampling methods were trained to predict the DA response. A soft voting ensemble classifier was used to achieve the final performance. The performance of the classifier was validated in the test set. RESULTS: The ensemble classifier showed an area under the curve (AUC) of 0.81 [95% confidence interval (CI), 0.74-0.87] in the training set. In the test set, the ensemble classifier showed an AUC, accuracy, sensitivity, and specificity of 0.81 (95% CI, 0.67-0.96), 77.8%, 78.6%, and 77.3%, respectively. The ensemble classifier achieved the highest performance among all the individual models in the test set. CONCLUSIONS: Radiomic features may be useful biomarkers to predict the DA response in prolactinoma patients.

Treatment Strategy for Giant Invasive Macroprolactinoma with Spontaneous Cerebrospinal Fluid Rhinorrhea: A Case Report and Literature Review.

BACKGROUND: Spontaneous cerebrospinal fluid (CSF) rhinorrhea associated with untreated prolactinomas is rare, which is in contrast to medical treatment-induced CSF rhinorrhea. Previous studies have suggested that cessation of drug administration should be the first line of treatment for prolactinoma with medically induced CSF rhinorrhea. On the other hand, there is no standard treatment strategy for prolactinoma with the development of spontaneous CSF rhinorrhea, because of its complicated pathology. Here, we report a case of giant invasive macroprolactinoma with spontaneous CSF rhinorrhea, and discuss the treatment strategy for this complicated condition with a review of the relevant literature. CASE DESCRIPTION: A previously healthy 39-year-old man presented with 1-year history of intermittent clear fluid nasal discharge with headache and vomiting. Magnetic resonance imaging showed a large parasellar mass with destruction of the skull base. This tumor was diagnosed as prolactinoma with hypopituitarism based on the results of hormone examinations. Tumor resection with skull base reconstruction in the endoscopic endonasal approach was performed because CSF rhinorrhea was aggravated by bromocriptine loading test and administration of dopamine agonist. Life-threatening bacterial meningitis occurred after surgery, which was cured with antibiotics along with resolution the CSF rhinorrhea. CONCLUSIONS: Careful consideration is necessary before applying standard first-line protocols with dopamine agonist administration in patients with prolactinoma, especially in cases with spontaneous CSF rhinorrhea. An appropriate treatment strategy should be planned according to the individual case, including factors such age, sex, pituitary function, tumor mass size, prolactin concentration, and condition of CSF leakage.