Cerebrospinal fluid (CSF) rhinorrhea is a rare complication after dopamine agonist treatment of macroprolactinomas. Up to 90% need surgical repair, however, there are controversial opinions on the necessity of tumor resection upon this occasion. Here we present our long-term follow-up experience in patients who underwent surgical repair of the CSF leak or observation.

We report a series of three patients who presented with cabergoline-induced CSF rhinorrhea with long-term follow-up up to 170 months. Two patients underwent endoscopic transnasal-transsphenoidal surgical repair of CSF rhinorrhea by fat graft and fibrin glue without tumor removal. In another patient, CSF rhinorrhea resolved spontaneously after two weeks without recurrence.

All three patients had no recurrence of CSF rhinorrhea during long-term follow-up up to 170 months. One patient with surgical CSF leak repair was asymptomatic with continued medication at long-term follow-up of 116 months. Tumor progression occurred 21 months after CSF leakage repair in another patient after cessation of dopamine agonist treatment and necessitated tumor debulking. The patient with continued medication without surgery had no recurrence of CSF rhinorrhea on long-term follow-up of 170 months.

The optimal management of CSF fistulae due to tumor shrinkage of macroprolactinomas after dopamine agonist therapy remains to be defined. Exceptionally, medication-induced CSF fistulae in response to tumor shrinkage may close spontaneously without recurrence. If persistent, transnasal-transsphenoidal closure of CSF fistulae represents an efficient treatment and dopamine agonist treatment may be continued. Thus, we recommend early surgical repair.

Issues: The clinical and paraclinical characteristics of prolactinomas differ mainly according to sex and tumor size. Drug treatment with dopamine agonists (ADs) has a crucial role in the management of prolactinomas. The use of surgery also has its indications. Purpose of the work: We aimed to establish the therapeutic strategy and the follow-up profiles of prolactinoma while analyzing the predictive factors of remission; we also looked for correlations between the size of the prolactinoma and the various clinical and paraclinical parameters. Materials and methods: This was a retrospective, descriptive, and analytical study of 77 cases of prolactinomas collected and monitored at the endocrinology and diabetology department of the Hedi Chaker CHU in Sfax between 2000 and 2017. Our patients were divided into three groups according to the size of their prolactinomas. Statistical correlations were sought between tumor size and clinical and biological parameters. Results: The mean age of our patients was 38.3 ± 14.2 years. The sample comprised 51 women (66.2%) and 26 men (33.7%). Anterior pituitary syndrome was observed in 75.3% of cases. The number of antehypophyseal deficits was significantly correlated with tumor size. Comparing the three groups, we noted that age, discovery circumstances, metabolic parameters, hypopituitarism, and pituitary extensions on imaging were significantly different. Therapeutically, our results showed that the favorable evolution of prolactinomas was correlated with tumor size and the duration of treatment. Conclusions: Tumor size appears to be a cornerstone in hormonal and radiological interpretation on the one hand and in the therapeutic decision on the other.

Opting for first-line surgery in carefully selected patients with microprolactinomas provides the advantage of avoiding long-term dopamine agonist (DA) medication and potential associated side effects. However, the lack of comprehensive long-term data poses a challenge in identifying those patients who would benefit the most from upfront surgery. To improve guidance in the selection process for microprolactinoma patients in clinical practice, we aimed to establish simple clinical and biochemical parameters predicting non-dependence on DAs.

Retrospective analysis of a prospectively maintained database, focusing on patients with microprolactinomas who underwent upfront surgery. We assessed clinical and biochemical risk factors for the patients' reliance on DAs at their latest follow-up using regression analysis. We next proceeded to conduct Receiver Operating Characteristic (ROC) analysis to determine the optimal threshold cutoff prolactin (PRL) level for practical application in clinical settings that best differentiates between surgical long-term remission status and long-term dependence on DAs.

A microadenoma was observed in 46 patients, of whom 12 (26%) exhibited long-term dependence on DAs at a median follow-up of 78 months. Baseline PRL values were significantly higher in patients with long-term DA dependence compared to those without (p = 0.05). High baseline PRL values (HR 23.9, 95% CI 1.0-593.7, p = 0.05), but not the presence of headache or male gender, were identified as independent predictors of long-term dependence on DAs. PRL thresholds for discriminating long-term DA dependence were estimated to be 290 µg/L (AUROC = 0.73, 95% CI 0.55-0.92, p = 0.03; sensitivity = 90%, specificity = 80%).

In patients with microprolactinomas, first-line surgery presents a favorable prospect for reducing reliance on DAs. However, for those with high PRL levels ≥ 290 µg/L at diagnosis, first-line surgery is not recommended, as the majority of them require adjuvant DA therapy in the long term.

Dopamine agonists (DAs), including cabergoline and bromocriptine, are the mainstay of treatment for prolactinomas. An underappreciated adverse effect associated with DAs is impulse control disorders (ICDs), characterized by the development of compulsive behaviors, including hypersexuality, pathological gambling, binge eating, and compulsive shopping, among others, which can negatively impact patients' and families' lives. This article reviews the prevalence, risk factors, presumed pathophysiology, and diagnostic and management strategies for ICDs in hyperprolactinemic patients treated with DAs.

Electronic literature searches were conducted to retrieve pertinent articles for inclusion in this article.

The reported prevalence of ICDs in patients with prolactinomas or hyperprolactinemia on DAs ranges from 7.5% to 46% across studies, with cabergoline being more commonly implicated than bromocriptine. Younger age, male sex, and specific genetic polymorphisms appear to increase the risk of ICDs. Diagnostic tools, such as the Minnesota Impulse Disorders Interview, the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease, the Barratt Impulsivity Scale-11, and computer-based tests, are instrumental in identifying ICDs. Patient education and periodic screening are advisable for early detection. Management strategies for patients who develop ICDs may include a decrease in DA dose or medication discontinuation, and psychiatric evaluation.

ICDs may occur in patients with hyperprolactinemia on DAs and negatively influence their lives if undetected. Further studies are needed to fully elucidate the risk factors and underlying mechanisms and to identify effective therapies for managing ICDs in patients with hyperprolactinemia on DAs.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-inherited syndrome involving multiple endocrine tumors. It is characterized by multiple mutations in the tumor suppressor gene MEN1, which is located on chromosome 11q13. As main etiology of MEN1 is genetic mutations, clinical symptoms may vary. In this editorial, we comment on the article by Yuan et al. This article describes a case of (MEN1) characterized by low incidence and diagnostic complexity. MEN1 commonly presents as parathyroid, pancreatic, and pituitary tumors. Diagnosis requires a combination of serologic tests, magnetic resonance imaging, computed tomography, endoscopic ultrasonography, immunologic and pathology. The diagnosis is unique depending on the site of disease. Surgical resection is the treatment of choice for MEN1. The prognosis depends on the site of origin, but early detection and intervention is the most effective.

This study aimed to investigate the prevalence of macroprolactinemia and the changes in hyperprolactinemia status over time among hyperprolactinemic patients in the Turkish population.

A retrospective study was conducted on 3,013 patient records from a central university hospital between October 2023 and October 2024. Of these, 634 hyperprolactinemic samples (Prolactin >15.2 μg/L in males, >23.3 μg/L in females) were analyzed using polyethylene glycol (PEG) precipitation method. Post-PEG prolactin levels were measured using electrochemiluminescence immunoassay, with the recovery percentage (R%) calculated as the ratio of prolactin post-PEG precipitation to total prolactin, where R% values below 40 % were indicative of macroprolactinemia. The change in R% values was analyzed in 63 hyperprolactinemic patients who underwent restesting.

Macroprolactinemia prevalence was found as 5.67 % of hyperprolactinemic patients with no macroprolactinemia cases observed at PRL levels above 85.40 μg/L. Male patients had significantly higher R% values than females (p=0.003). In the gray zone (R%: 40-60), 29.03 % of patients were classified as truly hyperprolactinemic. Repeated tests after an average of four months showed stable R% values in most cases, with only two patients changing classification between macroprolactinemia and true hyperprolactinemia.

The prevalence of macroprolactinemia in hyperprolactinemic Turkish patients was relatively low. As prolactin values increase, true hyperprolactinemia is more commenly observed instead of macroprolactinemia. Short-term retesting for macroprolactinemia may not be necessary unless clinical conditions change significantly. Accurate diagnosis requires method-specific cutoffs and further prospective studies using gold-standard methods like gel filtration chromatography.

Many review articles have explored data regarding the coexistence of specific types of pituitary adenomas (PAs) and polycystic ovary syndrome (PCOS), particularly focusing on the potential pathogenesis of this intersection and overlapping features. However, a comprehensive evaluation encompassing the full spectrum of PAs and their association with PCOS remains lacking. This review aims to provide a broad assessment of the interactions between these entities, emphasizing pathophysiological mechanisms, clinical presentations, diagnostic challenges and therapeutic implications.

A comprehensive literature search was conducted in the PubMed/MEDLINE database, focusing primarily on publications from the years 2000 to 2024, while also including seminal papers from the 1950s. The reference lists of selected articles were also manually searched. Inclusion criteria encompassed review articles, retrospective studies, clinical trials, case reports and meta-analyses providing data on the pathogenesis, clinical features, diagnostic challenges and therapeutic approaches related to PCOS and different PAs.

PCOS and functioning PAs often exhibit overlapping clinical features, complicating diagnosis and management. PCOS may precede and delay the diagnosis of growth hormone (GH)-secreting adenomas. The prevalence of PCOS or its features in acromegaly is influenced by disease activity, while approximating 13% in cases with controlled disease. Excess GH and insulin-like growth factor 1 (IGF-1) adversely affect ovarian function through direct pathways and by inducing insulin resistance, contributing to acromegaly-associated PCOS. In Cushing's syndrome (CS), findings consistent with PCOS may be present in 46% of patients, with cortisol excess contributing to menstrual dysfunction, hyperandrogenism and insulin resistance. While the prevalence of PCOS in patients with prolactinomas remains under-researched, recent studies indicate a 2.8%-10% prevalence of prolactinomas in PCOS. Elevated prolactin (PRL) levels in these patients may promote insulin resistance, further contributing to PCOS pathogenesis. Moreover, increased androgen bioavailability may be observed in all three aforementioned adenomas. To date, no studies have provided prevalence data for PCOS in other types of PAs.

Distinct clinical features, along with biochemical evaluations and imaging, can help differentiate the presence of both PAs and PCOS. Moreover, excluding other mimicking disorders is essential for an accurate diagnosis of PCOS. The persistence or recurrence of menstrual dysfunction, hyperandrogenism and metabolic disturbances in patients with controlled functioning adenomas may indicate a coexisting PCOS diagnosis. Timely diagnosis may optimize management and improve long-term outcomes for both conditions. Future studies should focus on investigating the clinical differences between patients with co-occurring PCOS and PAs compared to those with PCOS alone, ideally in larger cohorts, to better understand unique diagnostic and therapeutic considerations.

Background/Objectives: Giant pituitary adenomas (GPAs) pose significant surgical challenges due to their large size, parasellar/suprasellar extensions, and proximity to critical neurovascular structures. Although the endoscopic endonasal approach (EEA) is preferred for pituitary tumors, achieving gross total resection (GTR) in GPAs remains difficult. Additional transcranial approaches may improve resection rates while minimizing morbidity. This study evaluates the impact of endoscopic and combined surgical approaches on resection outcomes using a classification system previously defined in GPA patients treated over the past year. Methods: Among 517 pituitary adenomas treated in our clinic between September 2023 and September 2024, 49 GPA patients underwent endoscopic endonasal, transcranial, or combined surgery. Their medical records and surgical videos were retrospectively reviewed. Data included demographics, symptoms, imaging, surgical details, and follow-up outcomes. Tumor resection rates were analyzed based on the "landmark-based classification", considering radiological and pathological features and surgical approach. Results: The mean age was 45.5 years (female/male: 14/35). Zone distribution was 8 (Zone 1), 21 (Zone 2), and 20 (Zone 3). GTR was achieved in 34.6%, near-total resection in 36.7%, and subtotal resection in 28.5%. Endoscopic surgery was performed in 41 patients, combined surgery in 7, and a transcranial approach in 1. Complications included diabetes insipidus (9/49), cerebrospinal fluid leakage (2/49), apoplexy (2/49), hypocortisolism (3/49), epidural hematoma (1/49), and epistaxis (1/49). Conclusions: While EEA is effective for Zone 1 and 2 GPAs, Zone 3 tumors often require combined or transcranial approaches for better resection. A multimodal strategy optimizes tumor removal while minimizing morbidity. Individualized surgical planning based on tumor classification is crucial for improving outcomes.

Recent trends in first-line transsphenoidal surgery (TSS) for prolactinoma patients aim to reduce long-term dependence on dopamine agonists (DA). Key factors linked to poor surgical outcomes include cavernous sinus invasiveness and high baseline serum prolactin (PRL) levels. Defining simple PRL threshold values to indicate invasiveness and inform treatment strategy is crucial. In this retrospective cohort study of 149 prolactinoma patients treated with first-line transsphenoidal surgery (TSS) or dopamine agonist (DA) therapy, we evaluated preoperative prolactin (PRL) levels and cavernous sinus invasion as factors associated with long-term remission. Bayesian modeling identified cohort-wide and gender-specific PRL thresholds associated with invasiveness. Preoperative PRL values strongly correlated with cavernous sinus invasion (AUROC = 0.95; 95% CI: 0.90-0.98). The cohort-wide PRL threshold was 431.9 µg/L (95% CI: 181.1-708.3 µg/L), with gender-specific thresholds of 280.8 µg/L (95% CI: 51.0-528.2 µg/L) for women and 1325.0 µg/L (95% CI: 667.2-2582.9 µg/L) for men. Female thresholds were lower and less affected by age and obesity, while male thresholds were influenced by these factors, particularly in young, obese men. These findings suggest that gender-specific PRL thresholds may be useful for improving specificity and sensitivity in identifying invasiveness, potentially aiding clinical decisions. Personalized treatment informed by preoperative biomarkers is essential for optimizing outcomes and reducing DA reliance, but it should be considered in conjunction with a comprehensive clinical evaluation.

For several decades, dopamine agonist therapy has been the mainstay of treatment for prolactinomas, with surgery generally considered a second line for cases failing medical therapy due to intolerance or resistance. There is increasing recognition of the burden of long-term DA therapy; many patients experience debilitating side effects, and emerging evidence demonstrates that the prevalence of impulse control disorders has been vastly underreported. Long-term DA therapy is associated with significant costs to patients and healthcare systems, which is projected to exceed that of surgery in many circumstances. Recent advancements in surgical approaches, including endoscopic transsphenoidal surgery, have led to improved surgical outcomes (82-100% remission rates; serious complication rates < 2%), prompting a reappraisal of the role of surgery for prolactinoma. Favourable surgical outcomes have been observed in both remission and complication rates for microprolactinomas and well-circumscribed macroprolactinomas, leading to consideration of surgery as an earlier, or first-line, option in the treatment paradigm. Potential advantages of surgical management should be weighed against institutional case volume and expertise, the risk of perioperative complications, and the need for adjuvant medical therapy post-operatively. Ultimately, patients and care-providers should engage in shared decision-making following informed discussion about the risks and benefits of both medical and surgical approaches.

Prolactinomas (PRLs) are benign tumors with malignant characteristics that can invade the surrounding tissue structures and are challenging to treat. It has been reported that miR-21-5p expression in pituitary adenomas is correlated with tumor invasion and size. However, the mechanism of action of miR-21-5p in PRL remains unclear. Dysregulation of the phosphoinositide-3-kinase (PI3K) regulatory Subunit 1 pathway occurs frequently in cancer and plays an important role in tumor progression as an important component of the PI3K pathway. However, the role of PIK3R1 in PRL and its regulatory mechanism are unknown. In this study, we first explored the effect of miR-21-5p in PRL and then confirmed that PIK3R1 is a direct target of miR-21-5p using bioinformatics and cellular experiments. Subsequent in vitro experiments demonstrated that overexpression of PIK3R1 significantly attenuated the biological effects of miR-21-5p in PRL cells, such as promoting proliferation and invasion. Finally, we explored the mechanism by which PIK3R1 affects PRL progression and found that the inhibition of IκBa degradation by PIK3R1 impacts PRL progression via the miR-21-5p/PIK3R1/MMP pathway.

Data on pituitary neuroendocrine tumours (PitNETs) surgically treated during pregnancy are limited, and no studies have compared these cases to those treated in non-pregnant women. This study aimed to describe the clinical, radiological, and histological profiles of patients treated surgically for PitNETs during pregnancy and evaluate long-term prognosis.

This study was multicentric, observational, and retrospective.

We included 10 patients from 5 university hospitals who underwent surgical treatment for PitNETs during pregnancy or within 12 months postpartum, along with 30 matched non-pregnant controls treated surgically for PitNETs. Clinical and histological data, as well as progression-free survival without additional treatment, were compared between pregnant and non-pregnant patients.

Among the 10 PitNETs, 4 were corticotropic, 2 gonadotropic, 2 lactotropic, and 2 somatotropic. The primary surgical indication (tumour syndrome with or without failure of medical treatment) was similar between the two groups: 7/10 vs 19/30 (P = 1.00). There was no statistically significant difference in volume (P = .072) or radiological invasion markers (optic chiasm compression, P = .059, and cavernous sinus invasion, P = .274). However, PitNETs in pregnant women showed higher mitotic activity (P = .038) and were more frequently classified as grade 2b (Trouillas clinicopathological classification; P = .049). The need for second-line treatment was also more frequent (P = .005). PitNETs requiring surgical treatment during pregnancy are characterized by increased proliferative activity and progression after surgery. Despite this, the long-term prognosis remains favourable. These results need confirmation in a larger study.

Prolactinoma is the most common pituitary tumor, with clinical presentations varying according to sex, age of onset, tumor size, and prolactin (PRL) levels. These tumors are rare in the pediatric and adolescent populations. Hyperprolactinemia leads to hypogonadotropic hypogonadism, resulting in reproductive, metabolic, sexual, and skeletal consequences that can affect puberty development. Here, we present the case of a 23-year-old male patient diagnosed with arrested puberty secondary to a macroprolactinoma. The clinical presentation, diagnostic approach, therapeutic management, and a literature review are discussed.

In prolactinoma diagnosis, current guidelines recommend prolactin (PRL) assessment, considering values exceeding 200 ng/mL highly suggestive of prolactinoma. However, subtler hyperprolactinemia is more common, and to rule out potential prolactinomas, pituitary resonance magnetic imaging (MRI) studies are necessary. These present limitations in terms of availability, costs, and delays in diagnosis. We aimed to evaluate the screening utility of the metoclopramide (MCP) test in identifying patients with moderate hyperprolactinemia for whom MRI studies might be unnecessary.

We retrospectively selected patients with moderate hyperprolactinemia, with an MCP test and a pituitary MRI within the same assistance, and with no interfering pharmacological treatment. Increases in PRL (ΔPRLMax) and thyrotropin (ΔTSHMax) after MCP infusion were compared according to MRI findings: patients with microadenoma (<10 mm; n = 23), with macroadenoma (≥10 mm; n = 5), or without adenoma (n = 39).

ΔPRLMax exceeds baseline PRL capability to identify patients with an adenoma (area under the curve = 0.872 vs 0.776). ΔPRLMax below 220% identifies 100% of these patients with 71% of specificity. This screening would have avoided 42% of MRI, resulting in a cost savings of 34%. Analysis of ΔTSHMax only slightly increased specificity when considered as a secondary criterion. Test duration can be shortened to 30 min without compromising its screening capability.

A short MCP test is a useful and cost-effective screening tool to avoid unnecessary MRI. Its simplicity allows its performance in almost any clinical facility to easily rule out prolactinoma in an important percentage of patients, something of upmost importance especially in regions where MRI facilities or their access are limited.

Giant prolactinoma (size > 4 cm) is a rare condition and accounts for less than 1% of pituitary adenomas. In even rarer cases, these lesions may involve craniocervical structures requiring surgical intervention. The present case is the largest reported giant prolactinoma (99 × 72 × 57 mm). It led to cranial settling and significant central herniation at the foramen magnum, causing quadriparesis.

The patient was a 39-year-old Iranian man from a village around Hamadan city who presented with quadriparesis and paresthesia as well as loss of libido and impotence. Magnetic resonance imaging and computed tomography showed a huge diffuse avid enhancing infiltrating osteolytic lesion at the skull base. It had spread predominantly extramurally into the skull base resulting in cranial deposition, significant central herniation, myelopathy, and acute exacerbation of quadriparesis. On the basis of the pathology, immunohistochemistry, and elevated serum prolactin levels, the diagnosis of giant prolactinoma was almost definite. In addition to urgent midline suboccipital craniotomy for the central herniation and quadriparesis, he was treated with cabergoline followed by occiput cervical fixation and fusion to control the progressive subsidence.

Prolactinoma that is treatable with dopamine agonists should be considered as a differential diagnosis of skull base lesions, even those that are extradural, diffuse, and infiltrative. Giant prolactinoma can lead to craniocervical settling and central herniation that requires surgery and multidisciplinary management.

The widespread use of endoscope and increased surgical experiences in pituitary adenomas (PAs) has raised the expectations for higher resection and cure rates. The subject that will meet this expectation in all types of adenomas is the capsule and its dissection. The purpose of this study was to go beyond the commonly mentioned pseudocapsule definition for small-sized adenomas in previous studies and to describe the capsule structure in different morphologies present in pituitary adenomas of all sizes. This includes detailing the nuances of capsular dissection (CD) and presenting postoperative surgical outcomes through the experiences of a high-volume tertiary center.

In our center, 534 patients underwent endoscopic trans-sphenoidal surgery because of pituitary adenoma in 2022 by the same surgeon. The data of the patients were examined retrospectively. The surgical techniques applied were grouped as adenoma resection only, capsular resection after internal debulking, and direct extracapsular resection.

CD was performed in 275 (51.5%) patients. The gross total resection (GTR) rate in nonsecretory adenomas with and without CD was 90.7% (97/107) and 90.7% (97/107), respectively. The remission rate in secretory adenomas with and without CD was 81.0% (136/168) and 44.0% (67/152), respectively. When the patients were examined in 2 groups as those who underwent CD and those who did not, the application of CD had a positive predictive value in terms of GTR/remission ( P : .036). Capsule thickness was not found to be statistically significant depending on tumor subtype, size, and aggressiveness, but capsule thickness was statistically significant in terms of total capsular resection ( P : .045).

The morphology of the capsule, tumor size/subtype/consistency, and patient-specific factors are crucial for the selection of the surgical technique to be applied. It is possible to increase the GTR/remission rates in adenomas of all sizes by capsule dissection. Moreover, performing CD does not contribute significantly to the development of potential complications in such cases.

Empirical evidence for a low normal or reference interval for serum prolactin (PRL) is lacking for men, while the implications of very low PRL levels for human health have never been studied. A clinical state of "PRL deficiency" has not been defined except in relation to lactation. Using data from the European Male Ageing Study (EMAS), we analyzed the distribution of PRL in 3,369 community-dwelling European men, aged 40-80 years at phase-1 and free from acute illnesses. In total, 2,948 and 2,644 PRL samples were collected during phase-1 and phase-2 (3 to 5.7 years later). All samples were analysed in the same centre with the same assay. After excluding individuals with known pituitary diseases, PRL ≥ 35 ng/ml, and PRL-altering drugs including antipsychotic agents, selective serotonin reuptake inhibitors, or dopamine agonists, 5,086 data points (2,845 in phase-1 and 2,241 in phase-2) were available for analysis. The results showed that PRL declined minimally with age (slope = -0.02) and did not correlate with BMI. The positively skewed PRL distribution was log-transformed to a symmetrical distribution (skewness reduced from 13.3 to 0.015). Using two-sigma empirical rule (2[]SD about the mean), a threshold at 2.5% of the lower end of the distribution was shown to correspond to a PRL value of 2.98ng/ml. With reference to individuals with PRL levels of 5-34.9 ng/ml (event rate = 6.3%), the adjusted risk of developing type 2 diabetes increased progressively in those with PRL levels of 3-4.9 ng/ml: event rate = 9.3%, OR (95% CI) 1.59 (0.93-2.71), and more so with PRL levels of 0.3-2.9 ng/ml: event rate = 22.7%, OR 5.45 (1.78-16.62). There was also an increasing trend in prediabetes and diabetes based on fasting blood glucose levels was observed with lower categories of PRL. However, PRL levels were not associated with cancer, cardiovascular diseases, depressive symptoms or mortality. Our findings suggest that a PRL level below 3 ng/ml (64 mlU/l) significantly identifies European men with a clinically-important outcome (of type 2 diabetes), offering a lower reference-value for research and clinical practice.

Prolactinomas are the most prevalent type of pituitary neuroendocrine adenomas, primarily affecting women of reproductive age. Unlike other pituitary tumors, the first-line management has traditionally been pharmacological rather than surgical. This preference is due to the effectiveness of dopamine agonists (DAs), which typically reduce tumor size and normalize prolactin levels in most patients. However, this does not imply that there is no room for improvement; the duration of treatment and medication side effects often lead to compliance issues among patients. Recent advances in surgical techniques and molecular biology have paved the way for the development of precision medicine, allowing for more flexible and personalized treatment strategies for prolactinomas. This review aims to enhance clinical decision-making and patient care for endocrinologists by focusing on several key factors: predictive markers of DA sensitivity, clinical characteristics and suitability for transsphenoidal adenomectomy as a potential first-line treatment, factors determining the successful withdrawal of DAs after prolonged use, safety concerns during pre/post-pregnancy and breastfeeding, and determinants of tumor aggressiveness. Through tailored therapy-a patient-focused, multidisciplinary approach- we aim to improve the management of prolactinoma patients.

Prolactinomas account for more than half of pituitary adenomas, and besides their clinical impact on fertility and gonadal function, they lead to detrimental effects on bone. Patients with prolactinoma are prone to deterioration of bone structure caused not only by prolactin (PRL) induced hypogonadism but also by its direct actions on bone cells and calcium metabolism. However, clinical studies have shown inconsistent evidence regarding whether PRL could have a deleterious effect independently from gonadal insufficiency on skeletal integrity. Seminal studies from our group reported an increased prevalence of vertebral fractures (VFs) in both female and male patients with prolactinoma. Treatment of prolactinoma with dopamine agonists can restore gonadal function and improve bone mineral density. Since the presence of VFs may be related to more aggressive disease, bone comorbidities in prolactinoma should be managed by a multidisciplinary team in line with the recent concept of 'pituitary tumors centers of excellence'. The review aims to evaluate the mechanism of PRL actions on bone, as well as to provide practical indications for a modern approach to the management of skeletal complications of patients with prolactin-secreting adenoma considering different clinical characteristics and outcomes.

Erectile dysfunction (ED) is frequently underreported in men suffering from prolactinomas and can be challenging to manage. Both dopamine agonists (DAs) and transsphenoidal surgery (TSS) correct hyperprolactinemia and restore gonadal function. However, there is scarce data regarding their effectiveness in correcting ED over the long term.

This study is a retrospective single-center comparative cohort study analyzing men diagnosed with prolactinomas, both with and without confirmed erectile dysfunction (ED) at diagnosis. Independent risk factors for persistent ED over the long term were examined using multivariate logistic regression.

Among the 39 men with lactotroph adenomas, ED was one of the presenting symptoms in 22 (56%). The mean age at diagnosis was 45 ± 12 years. Surgery was the primary treatment in 6 (27%) ED patients and 8 (47%) non-ED patients. After a mean follow-up of 74 ± 48 months, remission from hyperprolactinemia was achieved in the majority (76%) of men: 71% in the non-ED cohort and 81% in the ED group (p = 0.70), regardless of the primary treatment strategy (surgical 84% versus medical 72%, p = 0.46). Long-term remission of ED was noted in 16 (73%) patients. Interestingly, high baseline BMI levels emerged as potential risk factors for persistent ED over the long term (OR 1.4, 95%CI 1.0-1.9; p = 0.04), while neither the initial adenoma size nor the primary treatment strategy (i.e., TSS vs. DAs) reached statistical significance.

Correcting hyperprolactinemia and its associated hypogonadism significantly improves ED in the majority of men with prolactinomas over the long term, regardless of the primary treatment strategy employed. In addition to addressing endocrine deficiencies, the early initiation of weight control programs may be considered for men with lactotroph adenomas and ED. Although our study suggests an association between BMI and the risk of persistent ED, further research is needed to establish any causal relationships.

Pituitary carcinoma is a rare entity comprising 0.1-0.2% of all pituitary tumors and presents significant diagnostic and therapeutic challenges. Intraspinal drop metastasis in these tumors is even rarer. We report a case of a prolactin secreting pituitary carcinoma with intracranial metastasis and multiple intraspinal drop metastasis. This is the first case where 68Gallium labelled [1,4,7,10 - tetraazacyclododecane - 1,4,7,10 - tetraacetic acid] -1- NaI3 - octreotide (68Ga-DOTANOC) whole-body positron emission tomography-computed tomography (PET-CT) has been used in a case of malignant prolactinoma, in an attempt to ascertain the somatostatin receptor (SSTR) expression on tumor cells. Through this paper, we suggest that SSTR targeted radionuclide therapy could have a potential role in aggressive pituitary tumors and pituitary carcinomas similar to the promising role of lutetium-labelled peptides in inoperable or metastasized gastroentero-pancreatic neuroendocrine tumors (GEP-NETs).

The results of many studies in recent years indicate a significant impact of pituitary function on bone health. The proper function of the pituitary gland has a significant impact on the growth of the skeleton and the appearance of sexual dimorphism. It is also responsible for achieving peak bone mass, which protects against the development of osteoporosis and fractures later in life. It is also liable for the proper remodeling of the skeleton, which is a physiological mechanism managing the proper mechanical resistance of bones and the possibility of its regeneration after injuries. Pituitary diseases causing hypofunction and deficiency of tropic hormones, and thus deficiency of key hormones of effector organs, have a negative impact on the skeleton, resulting in reduced bone mass and susceptibility to pathological fractures. The early appearance of pituitary dysfunction, i.e. in the pre-pubertal period, is responsible for failure to achieve peak bone mass, and thus the risk of developing osteoporosis in later years. This argues for the need for a thorough assessment of patients with hypopituitarism, not only in terms of metabolic disorders, but also in terms of bone disorders. Early and properly performed treatment may prevent patients from developing the bone complications that are so common in this pathology. The aim of this review is to discuss the physiological, pathophysiological, and clinical insights of bone involvement in pituitary disease.

Effective side effects management present a challenge in antipsychotic treatment with second-generation antipsychotics (SGAs). In recent years, most of the commonly used SGAs, except for clozapine, have been shown to differ only slightly in their effectiveness, but considerably regarding perceived side effects, safety profiles, and compatibility to preexisting medical conditions.

The current state of available evidence on side-effect management in SGA treatment of patients with schizophrenia spectrum disorders (SSD) is reviewed. In addition, current guideline recommendations are summarized, highlighting evidence gaps.

SGA safety and side effects needs to be considered in treatment planning. Shared decision-making assistants (SDMA) can support patients, practitioners and relatives to orient their decisions toward avoiding side effects relevant to patients' adherence. Alongside general measures like psychosocial and psychotherapeutic care, switching to better tolerated SGAs can be considered a relatively safe strategy. By contrast, novel meta-analytical evidence emphasizes that dose reduction of SGAs can statistically increase the risk of relapse and other unfavorable outcomes. Further, depending on the type and severity of SGA-related side effects, specific treatments can be used to alleviate induced side effects (e.g. add-on metformin to reduce weight-gain). Finally, discontinuation should be reserved for acute emergencies.

To identify differences in the presentation and surgical outcomes between very large (30-39 mm) and giant (≥ 40 mm) (LARGE group) pituitary adenomas (PAs) compared to the smaller group (< 30 mm) (non-LARGE group).

Eighty patients with very large (n = 44) or giant (n = 36) PAs and 226 patients in the non-LARGE group who underwent tumor resection by pituitary surgery between 2008 and 2023 were studied. Hormonal, radiological, ophthalmological, and pathological data, and surgical outcomes were evaluated.

Preoperatively, patients of the LARGE group presented more frequently with visual impairment (82.5% vs. 22.1%, P < 0.001) and with pituitary apoplexy (15.0% vs. 2.7%, P < 0.001) than the non-LARGE group. Moreover, the LARGE group were more commonly associated with preoperative panhypopituitarism (28.8% vs. 6.2%, P < 0.001). This group presented cavernous sinus invasion more frequently (71.3% vs. 23.9%, P < 0.001). The non-LARGE group achieved surgical cure more often than the LARGE group (79.7% vs. 50.0%, P < 0.001), and the rate of major complications was higher in the latest (8.8% vs. 1.3%, P < 0.004).

PAs ≥ 30 mm are most frequently accompanied by hormonal dysfunction, cavernous sinus invasion, and visual impairment. All this implies lower resection rates and higher postoperative complications than the smaller adenomas, posing a real surgical challenge.

To review experience regarding the treatment of prolactinomas by endoscopic endonasal surgery focusing on the association between presurgical dopamine agonist (DA) treatment and perioperative outcomes, surgical morbidities, endocrine outcomes, and pathological characteristics.

A single-center series of 290 cases was analyzed retrospectively and clinical data were collected. Intratumoral collagen content was assessed by Masson trichrome staining.

Tenacious tumor consistency (27.8% vs 9.8%, P < .001) was more common in DA-pretreated patients compared with patients who underwent initial surgery. Moreover, DA-pretreated macroadenomas presented more intraoperative blood loss (200 [100-400] mL vs 175 [100-300] mL; P = .014), longer surgical duration (177 ± 95 minutes vs 154 ± 57 minutes; P = .043), and more surgical morbidities (19.4% vs 8.9%; P = .034). Additionally, DA-pretreated macroadenomas presented a higher collagen volume fraction than that of the initial surgery group (23.6 ± 2.2% vs 13.2 ± 2.1%; P = .001). Correlation analysis revealed a close correlation between collagen volume fraction and the cumulative dose of bromocriptine (BRC) in macroadenomas (r = 0.438, P < .001). Regarding endocrine outcomes, DA-pretreated microadenomas showed a lower proportion of initial remission compared with patients who underwent initial surgery (86.7% vs 100%, P = .047).

This study described increased surgical difficulty and inferior endocrine outcomes associated with tumor fibrosis secondary to presurgical BRC treatment in prolactinomas. Neurosurgeons should note that presurgical BRC treatment may render subsequent surgery more challenging.

Pituitary adenomas are rare in children and young people under the age of 19 (hereafter referred to as CYP) but they pose some different diagnostic and management challenges in this age group than in adults. These rare neoplasms can disrupt maturational, visual, intellectual and developmental processes and, in CYP, they tend to have more occult presentation, aggressive behaviour and are more likely to have a genetic basis than in adults. Through standardized AGREE II methodology, literature review and Delphi consensus, a multidisciplinary expert group developed 74 pragmatic management recommendations aimed at optimizing care for CYP in the first-ever comprehensive consensus guideline to cover the care of CYP with pituitary adenoma. Part 2 of this consensus guideline details 57 recommendations for paediatric patients with prolactinomas, Cushing disease, growth hormone excess causing gigantism and acromegaly, clinically non-functioning adenomas, and the rare TSHomas. Compared with adult patients with pituitary adenomas, we highlight that, in the CYP group, there is a greater proportion of functioning tumours, including macroprolactinomas, greater likelihood of underlying genetic disease, more corticotrophinomas in boys aged under 10 years than in girls and difficulty of peri-pubertal diagnosis of growth hormone excess. Collaboration with pituitary specialists caring for adult patients, as part of commissioned and centralized multidisciplinary teams, is key for optimizing management, transition and lifelong care and facilitates the collection of health-related quality of survival outcomes of novel medical, surgical and radiotherapeutic treatments, which are currently largely missing.

Data regarding the presence of a prolactin (PRL) threshold above which a pituitary magnetic resonance imaging (MRI) is mandatory in patients with hyperprolactinemia (hyperPRL) are controversial and derived primarily from studies focused on female populations. Aim of our study was to evaluate in a cohort of patients of both sexes with confirmed hyperPRL, the possible correlation between PRL values and the presence of pituitary abnormalities.

We retrospectively analyzed data from patients who underwent serial PRL sampling at our Division between January 2015 and December 2022. Patients diagnosed with monomeric hyperPRL at serial sampling and with subsequent contrast-enhanced MRI results available for the pituitary region were included in the study. Exclusion criteria were prior pituitary disease, severe renal insufficiency, liver cirrhosis, uncompensated primary hypothyroidism and ongoing therapy with hyperprolactinemic drugs. Physiological causes of hyperPRL were also ruled out.

Out of the 1253 patients who underwent serial PRL sampling, 139 patients (101 women and 38 men) met the inclusion criteria: 106 (76.3%) patients had some form of pituitary disease, with microlesions observed in 69.8%, macrolesions in 25.5% and other findings in 4.7% of subjects. PRL values showed a modest accuracy in predicting the presence of a pituitary abnormality and the best cut-offs identified were >25 µg/L (AUC 0.767, p = 0.003) and >44.2 µg/L (AUC 0.697, p < 0.001) in men and women, respectively; however, if only patients with PRL values > 500 µg/L were excluded from the analysis, as they were already supposed to harbor a macroprolactinoma, PRL levels were not able to predict the presence of a macrolesion neither in men nor women.

Given the high prevalence of pituitary abnormalities in patients of both sexes with hyperPRL at serial sampling, performing a pituitary imaging in all cases of hyperPRL, even if mild, appears to be a cautious choice.

Prolactinomas-pituitary tumors that overproduce prolactin-can cause various troublesome symptoms. Dopamine agonists (DAs) reduce prolactin production in the prolactin pathway, making them the first-line treatment for prolactinomas. However, the main side effect of DA treatment, hyperdopaminergia, is an explicit etiology for psychiatric side effects. Psychiatric conditions are often treated with dopamine antagonists, which can induce hyperprolactinemia. This presents a challenge for patients with both a prolactinoma and a preexisting psychiatric condition, as treatment of one condition could worsen the other. This review seeks to identify an adequate therapeutic regimen for patients with coexisting prolactinomas and psychiatric symptoms.

This review examined PubMed citations from 1960 to 2023 published in English and involving human subjects. Case reports, case series, and cohort studies involving patients with concomitant prolactinomas and psychiatric symptoms, as validated by brain imaging, serologic prolactin levels, and medical history or chart reports of psychiatric symptoms, were included.

Thematic analysis included 23 reports involving 42 participants; 27 of the 42 patients experienced a significant reduction in prolactin levels and psychiatric symptoms (64%). Treatment of those 42 patients included discontinuing or altering antipsychotic/dopamine antagonist therapy or discontinuing DA therapy to reduce psychiatric symptoms, with surgery or radiation postpharmacotherapy as a last-line strategy. However, in some cases (reported in Tables 2 to 4), either psychiatric or prolactin-related symptoms recurred despite adjustment.

Clinicians may find it beneficial to prioritize specific antipsychotics (aripiprazole, olanzapine, ziprasidone, or clozapine) over others (risperidone, thioridazine, thiothixene, and remoxipride). Discontinuing DA medication at least periodically until the patient's condition improves may also be advisable. If these 2 initial approaches do not yield a significant improvement in symptom management, surgery or radiation therapy may be considered. As patients may respond differently to these therapies, our study still recommends a patient-centered approach.

Prolactin-producing pituitary tumor (PRLoma) is the most prevalent functional pituitary tumor. If the tumor becomes large, vision can be impaired. In contrast to other pituitary tumors, cabergoline (CAB) is extremely effective for PRLoma and has become the first-line treatment. In this study, we examined our experience with the pharmacological and surgical management of PRLomas with visual impairment (VI) to determine whether VI could be a surgical indication. Further, we discussed the function of surgery in situations where the gold standard of PRLoma treatment was CAB administration. Of the 159 patients with PRLomas (age, 13-77 [mean = 36.3] years; men, 29; women, 130) at Tokyo Women's Medical University Hospital from 2009 to 2021, 18 (age, 15-67 [mean = 35.8] years; men, 12; woman, 6) had VI (subjectively, 12; objectively, 6). They started CAB treatment immediately (maximum dose: 0.5 to 6 mg/week; average: 2.17 mg/week). VI improved in 16 patients (88.9%) but did not improve in 2 (11.1%) requiring surgeries. One of the two patients had a parenchymal tumor resistant to CAB, and the other had a cystic tumor due to intratumoral bleeding. Consequently, CAB is the first-line treatment for PRLomas with VI because of its significantly high rate of improvement. However, close and rigorous surveillance is necessary for cases resistant to CAB, and the correct decision is required regarding surgical interventions at proper timing and appropriate surgical approaches considering the purpose of surgery.

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.

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.

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.

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.

Among the patient population in Basrah, Iraq, prolactinoma is the most commonly found pituitary tumor. Impulse control disorders (ICDs) were reportedly associated with these patients being treated with cabergoline. This study aimed to assess the prevalence of ICDs in cabergoline-treated prolactinoma patients versus healthy, matched controls.

This cross-sectional case-control study was conducted at the Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) in Basrah, southern Iraq, from January 2023 to May 2023. It included 30 cabergoline-treated prolactinoma patients and 30 healthy, matched controls. The questionnaire for ICDs in Parkinson's disease was used as a screening tool. Following this, positively screened patients were evaluated using validated criteria accordingly to diagnose impulse control disorders.

The ICDs were diagnosed in nine (30%) cabergoline-treated prolactinoma patients versus two (6.7%) in control (p = 0.02). The most frequent ICD types were hypersexuality and binge eating, while no patient reported pathological gambling. Three patients reported multiple types of ICDs. The patients' sociodemographic characteristics, prolactinoma duration and size, and cabergoline dose did not correlate significantly with ICD diagnosis.

Treatment with cabergoline is associated with the development of ICDs. Therefore, clinicians should be aware of this disabling side effect to ensure its early detection and treatment.

This research investigates the utility of Chat Generative Pre-trained Transformer (ChatGPT) in addressing patient inquiries related to hyperprolactinemia and prolactinoma. A set of 46 commonly asked questions from patients with prolactinoma were presented to ChatGPT and responses were evaluated for accuracy with a 6-point Likert scale (1: completely inaccurate to 6: completely accurate) and adequacy with a 5-point Likert scale (1: completely inadequate to 5: completely adequate). Two independent endocrinologists assessed the responses, based on international guidelines. Questions were categorized into groups including general information, diagnostic process, treatment process, follow-up, and pregnancy period. The median accuracy score was 6.0 (IQR, 5.4-6.0), and the adequacy score was 4.5 (IQR, 3.5-5.0). The lowest accuracy and adequacy score assigned by both evaluators was two. Significant agreement was observed between the evaluators, demonstrated by a weighted κ of 0.68 (p = 0.08) for accuracy and a κ of 0.66 (p = 0.04) for adequacy. The Kruskal-Wallis tests revealed statistically significant differences among the groups for accuracy (p = 0.005) and adequacy (p = 0.023). The pregnancy period group had the lowest accuracy score and both pregnancy period and follow-up groups had the lowest adequacy score. In conclusion, ChatGPT demonstrated commendable responses in addressing prolactinoma queries; however, certain limitations were observed, particularly in providing accurate information related to the pregnancy period, emphasizing the need for refining its capabilities in medical contexts.

Pituitary adenomas are benign tumors of the anterior portion of the pituitary gland (adenohypophysis), representing the 25% of all the tumor alterations. Pituitary adenomas are classified by the type of hormone secreted, cellularity, size, and structural alterations by the hormonal segregation. The diagnosis consists on the histopathological identification of cell types and the image-guided by magnetic resonance or tomography; the treatment can be both pharmacological and surgical. Metabolic Syndrome is the set of clinical conditions that increase the risk of cardiovascular diseases with an estimated prevalence of 25% worldwide. The alterations of metabolic syndrome are obesity, hypertension, dyslipidemia, insulin resistance, and diabetes mellitus type II. Pituitary adenomas and metabolic syndrome have an important relationship, hormone-secreting by pituitary adenomas affects a myriad of signaling pathways, which allows a favorable environment for the appearance of the metabolic syndrome. Moreover, patients with pituitary adenomas are shown to have an improvement in metabolic parameters after the medical/surgical treatment. The objective of this review is to explore the possible mechanisms through which PAs contributes to MetSx.

The primary aim of this study was to identify predictive factors associated with onset of de-novo clinically significant pituitary insufficiencies following endoscopic endonasal surgery (EES) for pituitary adenomas. The secondary objective explored the predictive factors of surgical success.

A retrospective analysis was conducted on 211 patients who underwent EES. Logistic regression models were employed for the primary and secondary objectives. Patients were stratified into specific groups based on surgical indications and prolactin levels for nuanced analysis.

Significant predictors for de-novo pituitary insufficiencies included male sex (OR 3.3, CI95% 1.3-8.1, p=0.01), immediate postoperative insufficiencies (OR 5.6, CI95% 2.8-11.1, p<0.001), and HYPRONOS criteria (OR 5.7, CI95% 1.6-20.9, p=0.008). For surgical success, preoperative insufficiencies (OR 0.7, CI95% 0.5-0.9, p=0.008), repeat surgeries (OR 0.1, CI95% 0-0.4, p=0.001), and gonadotroph or somatotroph adenomas were significant. Age and adenoma size were not predictive in multivariate analysis. Furthermore, we observed a "dip and recover" effect of prolactin after surgery and lower prolactin levels at follow-up (< 3 ng/ml) are correlated with more anterior pituitary insufficiencies than normoprolactinemic patients (p = 0.004).

This study identifies key predictors for outcomes in pituitary surgery. Our research is the first to employ individualized success criteria for EES, challenging existing perceptions about the role of age and adenoma size. These findings open avenues for nuanced, individualized preoperative risk assessment and postoperative management.

To compare the predictive abilities of two frailty indices on post-operative morbidity and mortality in patients undergoing pituitary adenoma resection.

The National Surgical Quality Improvement Program (NSQIP) database was used to retrospectively collect data for patients undergoing pituitary adenoma resection between 2015-2019. To compare the predictive abilities of two of the most common frailty indices, the 5-point modified frailty index (mFI-5) and the risk analysis index (RAI), receiver operating curve analysis (ROC) and area under the curve (AUC)/Cstatistic were used.

In our cohort of 1,454 patients, the RAI demonstrated superior discriminative ability to the mFI-5 in predicting extended length of stay (C-statistic 0.59, 95% CI 0.56-0.62 vs. C-statistic 0.51, 95% CI: 0.48-0.54, p = 0.0002). The RAI only descriptively appeared superior to mFI-5 in determining mortality (C-statistic 0.89, 95% CI 0.74-0.99 vs. Cstatistic 0.63, 95% CI 0.61-0.66, p=0.11), and NHD (C-statistic 0.68, 95% CI 0.60-0.76 vs. C-statistic 0.60, 95% CI: 0.57-0.62, p=0.15).

Pituitary adenomas account for one of the most common brain tumors in the general population, with resection being the preferred treatment for patients with most hormone producing tumors or those causing compressive symptoms. Although pituitary adenoma resection is generally safe, patients who experience post-operative complications frequently share similar pre-operative characteristics and comorbidities. Therefore, appropriate pre-operative risk stratification is imperative for adequate patient counseling and informed consent in these patients. Here we present the first known report showing the superior discriminatory ability of the RAI in predicting eLOS when compared to the mFI-5.

Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma.

This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies.

The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost.

The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that.

Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.

The management of giant pituitary adenomas (GPAs) is challenging due to associated endocrinopathies and the close proximity of these tumors to critical structures, such as the optic nerves, structures of the cavernous sinus, and hypothalamus. The objective of this review article was to summarize the current management strategies for giant pituitary adenomas, including the role of open and endoscopic surgical approaches and the role of medical and radiation therapy in conjunction with surgery.

We conducted a retrospective review of GPAs operated at our institute between January 2010 and March 2023. Surgical approaches, extent of resection, and associated complications were documented. Furthermore, we conducted a thorough literature review to identify relevant studies published in the past decade, which were incorporated along with insights gained from our institutional case series of GPAs to analyze and integrate both the existing knowledge base and our institution's firsthand experience in the management of GPAs.

A total of 46 giant pituitary adenomas (GPAs) were operated on, using various surgical approaches. Transsphenoidal approach was used in 25 cases and a staged approach using transsphenoidal and pterional was used in 15 cases. Other approaches included transcortical-transventricular, transcallosal, pterional/orbitozygomatic, and subfrontal approaches. Complications and technical nuances were reported.

The management of giant pituitary adenomas remains complex, often involving several modalities-open or endoscopic resection, radiosurgery, and medical management of both the tumor and associated endocrinopathies. Surgical resections are often challenging procedures that require careful consideration of several factors, including patient characteristics, tumor location, and size, and the experience and skill of the surgical team.

The most common type of functioning pituitary adenomas is prolactinomas; unlike other types, they are treated medically with dopamine agonists (DA). This treatment aims to normalize PRL levels and decrease tumor size by 50% or more. These objectives are typically achieved by 90% of patients with microprolactinoma, two-thirds of those with macroprolactinomas, and about half of those with giant prolactinomas. Life-long pharmacological treatment implies costs, discomfort, and the possibility of side effects, therefore, it has been suggested that DA discontinuation could be attempted in some patients. Long-term remission seems more likely in who, after 2 years of therapy achieve clinical, biochemical, and imaging remission criteria: no evidence of hypogonadism, a normal PRL level (preferably <5 ng/mL), and a >50% of tumor size reduction. Long-term remission seems to be more likely if the patient has been treated with cabergoline (CBG) for a minimum of 2 years, the PRL levels have normalized, tumor size has decreased by at least 50%, and the DA dose can gradually be tapered down to 0.25-0.5 mg per week. After treatment withdrawal, about 65% of patients experience a recurrence of hyperprolactinemia within the first 12 months of DA discontinuation. Although in most patients in whom DA discontinuation has been attempted, the hyperprolactinemia will recur, not all of them will require re-initiation of treatment. A good clinical judgement is crucial to identify those patients who need life-long treatment.