Background: Nowadays, pituitary gland tumors are increasingly recognized as common disorders, accounting for up to 25% of intracranial neoplasms. Mentioned repeatedly there are not many studies investigating the updated and larger epidemiology of pituitary gland tumors studies are needed. Methods: This study employed a descriptive observational study design with a retrospective approach using secondary data from medical records of patients diagnosed with pituitary gland tumors at Dr. Soetomo General Hospital Surabaya from January 2019 – December 2023. Results: A total of 193 patients met the inclusion criteria. Variables studied included age, gender, demographic origin, clinical manifestations, blood hormone levels, radiological imaging, histopathology, immunohistochemistry, and patient management. Conclusions: Among the patients, 56.5% are females, with the largest age group being 51–60 years (24.9%), and most patients resided in East Java Province outside Surabaya City (61.1%). Most common clinical manifestations were visual disturbances (66.3%), headache (58.3%), and nausea–vomiting (16%). About 31,1% of patients presented with hormone-related manifestations. Laboratory examination of blood hormone levels showed the following results: non-functioning pituitary adenoma (51.8%), prolactinoma (39.4%), gonadotroph adenoma (2.1%), somatotroph adenoma (2.1%), TSH-producing tumor (1%), and cortisol-producing tumor (6.6%). examination of pituitary tumors was most commonly performed using MRI, showing lesions with a diameter ≥10 mm, well-defined margins, regular borders, solid components, and no calcification. Histopathological findings revealed that most of the samples were pituitary adenomas (94.3%), with only one case of pituitary carcinoma identified. The most commonly used pharmacological treatments were CRIPSA (22.8%), dexamethasone (21.2%), and euthyroxine (10.6%), Most frequent surgical management was Endoscopic Transsphenoidal Surgery (70.4%).

The safety of testosterone replacement therapy (TRT) has generated some controversy during recent years. While untreated hypogonadism leads to diminished sexual characteristics, muscle weakness and osteoporosis, the cardiovascular (CV) safety of TRT has been vigorously debated. TRT remains the standard of care for those with secondary hypogonadism (SHG) due to structural pituitary disease, but long-term CV safety in this population remains unclear. We conducted a retrospective cohort study to investigate occurrence of major adverse cardiovascular events (MACE) in male patients with non-functioning pituitary adenomas and prolactinomas, with and without SHG. Demographic data, TRT treatment, stroke, myocardial infarction, and mortality data were retrieved from chart review as well as provincial cardiac and stroke registries. There were 408 patients followed for a median 8.1 years (IQR 3.3-14.1); 150 (36.7%) did not have SHG, while 214 (52.5%) had SHG adequately treated with TRT and 44 (10.8%) had SHG that was untreated. Multivariable logistic regression analysis demonstrated no significant difference in MACE between groups. MACE outcomes were not impacted by size of adenoma, presence of other pituitary hormonal deficits, or testosterone levels. There was increased risk of mortality in untreated SHG compared to both TRT-treated SHG and those without SHG. TRT does not appear to increase risk of MACE in those with SHG related to pituitary disorders. Untreated SHG appears to convey increased risk of mortality though these patients were older and more comorbid.

Pituitary prolactinoma, the most prevalent functional pituitary adenomas, has witnessed significant advancements in diagnostic and therapeutic concepts with the advancement of surgical techniques and the update of more clinical evidence-based medical evidence. Based on the 2014 version of the "Chinese Consensus on the Diagnosis and Treatment of Pituitary Prolactin Adenoma", the China Pituitary Adenoma Specialist Council has revised this consensus, in accordance with the latest evidence-based medical evidence and clinical experience, aiming to provide standardized diagnosis and treatment suggestions for clinicians. The consensus systematically expounds the epidemiological characteristics, clinical manifestations, diagnostic criteria, differential diagnosis process and treatment strategies of prolactinomas, and puts forward individualized management suggestions for special populations (such as pregnant women, male patients and refractory prolactinomas). The treatment decision strongly advocates for multidisciplinary team evaluation involving specialists from neurosurgery, endocrinology, radiology, radiation oncology, pathology, ophthalmology, and obstetrics/gynecology, etc. Through the raising of recommendation questions, summary and evaluation of evidence, formation of recommendation opinions, expert discussions, and in combination with clinical practice, 36 recommendations have been formed in aspects such as screening, assessment, diagnosis, treatment, and monitoring. This consensus takes into account both clinical needs and international evidence-based standards, providing a highly reliable reference for diagnosis and treatment, and is expected to enhance the standardization and overall level of prolactinoma diagnosis and treatment in China.

Pituitary prolactinoma is the most common functioning pituitary adenoma in clinical practice. Hypogonadotropic hypogonadism secondary to hyperprolactinemia is the main clinical manifestation of patients. Most patients respond well to dopamine receptor agonists (DA). The patients with DA resistance and pituitary tumor apoplexy need neurosurgical treatment. Neurosurgery also increasingly applied to non-invasive microadenoma patients. Radiotherapy is an effective adjuvant treatment method. However, 10%-15% of prolactinoma patients develop refractory pituitary tumors and even progress to metastatic pituitary neuroendocrine tumors (pituitary cancer), seriously affecting the quality of life and even lifespan of patients. This article systematically reviews the definition evolution, molecular mechanism, early predictive markers, and the latest treatment progress of refractory pituitary prolactinoma. It is also suggested that the diagnosis and treatment level of refractory pituitary prolactinoma be gradually improved through the exploration and application of precision medicine and the promotion of standardized multidisciplinary collaborative diagnosis and treatment models.

Recently, the therapeutic paradigm for pituitary prolactinomas has shifted from a single-pathway of "drug priority" approach toward a multidisciplinary assessment and individualized treatment model. The "Consensus on the diagnosis and treatment of pituitary prolactinoma(2025 edition)" combines the latest evidence-based medicine and technological advances at home and abroad to expand the indications and clinical role of surgical intervention. This article systematically reviews the major differences between the two versions of consensus regarding surgical recommendations, highlighting that with the widespread adoption of endoscopic transnasal techniques, surgery is now recognized as a first-line or co-primary treatment option in selected patients, particularly for those with well-circumscribed microadenomas, macroadenomas, and women of reproductive age. In addition, the article further discusses the role of surgery in fertility management, long-term remission, and in cases with poor drug tolerance or adherence. It also emphasizes that the surgen's experience, technical proficiency, and multidisciplinary collaboration are still the key prerequisites for ensuring the safety and effectiveness of treatment. The publication of the 2025 consensus marks a major conceptual shift in the management of prolactinomas, offering important guidance and practical paths for establishing a more precise, effective, and humanistic comprehensive diagnosis and treatment system.

Pituitary prolactinoma is a common functional pituitary tumor with a high incidence in women of childbearing age, and its diagnosis and treatment are closely related to obstetrics and gynecology practice. "Consensus on the diagnosis and treatment of pituitary prolactinoma (2025 edition)" is based on evidence-based medicine and proposes systematic solutions to obstetrics and gynecology problems such as menstrual disorders, infertility, pregnancy safety, and lactation management. By constructing the path of abnormal menstruation-infertility assessment-pregnancy monitoring-postpartum management, a prolactinoma management model with obstetrics and gynecology needs as the main line is established. According to the high-quality evidence, it breaks through the traditional tumor-centered model and emphasizes the equal importance of reproductive health protection and tumor control. At the same time, the consensus clarifies the symptom-driven diagnostic pathway of obstetrics and gynecology (such as abnormal menstruation as an absolute indication for prolactin testing), the dynamic balance strategy of fertility management (such as microadenoma patients can try pregnancy during dopamine agonist therapy and stop the drug after pregnancy), a symptom-led monitoring system during pregnancy, postpartum management to support lactation, and a simplified long-term follow-up plan. It emphasizes the important role of obstetrics and gynecology in multidisciplinary diagnosis and treatment, providing a standardized and individualized decision-making framework for clinical practice.

Prolactinoma, the most common functional pituitary neuroendocrine tumor, belongs to Pit-1 lineage of pituitary neuroendocrine tumors. The treatment methods include surgery, medication, and radiation therapy, with drug therapy centered around dopamine receptor agonists. Cabergoline, a selective D2 receptor agonist with high receptor affinity and long-acting properties, is recommended as a first-line treatment in international guidelines for prolactinoma management.Based on the 2014 edition, the "Consensus on the diagnosis and treatment of pituitary prolactinoma (2025 edition)" has made important updates to the treatment recommendations for cabergoline, mainly including: For patients with bromocriptine resistance, if cabergoline is available, switching to cabergoline is recommended as the first choice; For patients receiving long-term, high-dose cabergoline treatment, regular echocardiogram monitoring is recommended to assess the condition of heart valves. Meanwhile, it also provides more detailed elaborations on cabergoline's efficacy, adverse reactions (such as heart valve disease, impulse control disorders, etc.), and its application in drug-resistant prolactinomas. However, since cabergoline has not yet been marketed in Chinese mainland, the practical clinical experience with this drug in the domestic setting remains relatively limited, and there is a lack of systematic summary of local data. Endocrinologists need to pay special attention to the selection of its indications, efficacy evaluation, and safety monitoring during long-term medication.

The "Consensus on the diagnosis and treatment of pituitary prolactinoma (2025 edition)" is based on the latest evidence-based medicine evidence and has comprehensively refined the diagnosis and treatment strategies for prolactinoma. In terms of diagnosis, the consensus optimizes the imaging evaluation process and introduces innovative recommendations such as aneurysm screening. In terms of treatment, the consensus clarifies a step-by-step medication strategy, establishes the important position of neuroendoscopic surgery for well-defined adenomas with Knosp 0-1 grade, and refines the application details of radiotherapy. In terms of the management of special populations, the consensus significantly strengthens the refined and individualized management plans for refractory prolactinoma, male patients, pregnant patients, etc. The artical vertically compars the evolution of the 2025 edition consensus with the 2014 edition consensus, horizontally compars its similarities and differences with international consensus, and deeply explores the clinical value and current limitations of the new edition consensus, in order to provide references for clinical practice and jointly promote the improvement of the diagnosis and treatment level of prolactinoma in China.

BackgroundWe have recently shown that estrogen‐induced prolactin‐secreting pituitary tumors are aggressive in prenatal alcohol‐exposed female rats. In this study, we investigated whether similar tumor aggressiveness occurs in estrogen‐treated prenatal alcohol‐exposed male rats.MethodsPregnant Fischer 344 rats were fed from gestational days 7 and 21 with a liquid diet containing ethanol 6.7% v/v (AF), pair‐fed with an isocaloric liquid diet (PF), or fed chow ad libitum (AD). Alcohol‐fed dams exhibited a blood alcohol concentration of 120–150 mg/dL 2 h after the last feeding. Male offspring were orchiectomized at 60 days of age and implanted subcutaneously with estradiol implants. Four months after the estradiol implants, rats were sacrificed, and pituitary tumor tissues were collected. Tumor cells were isolated and cultured for analysis.ResultsPituitary tumor cells from AF males exhibited stem‐like cell properties and showed elevated expression of stem cell regulatory genes and proteins (SOX‐2, OCT‐4, KLF4, SNAIL‐1, and Nestin), tumor aggressiveness markers (MMP‐9, CD44, CD34, PTTG, FGFR4, Ki‐67, N‐Cadherin), and prolactin compared to those from AD and PF controls. AF cells also had a higher cell proliferation rate, increased invasiveness, and colony formation compared to those in AD and PF cells, indicating more aggressive cancer cells than control cells. Notably, AF cells had a higher expression of developmental pluripotency‐associated 4 (Dppa4), a gene we recently identified as upregulated in aggressive tumors and in fetal alcohol‐exposed animals.ConclusionsThese findings are consistent with our previous observations in estrogen‐treated AF female rats. These results support the hypothesis that prenatal alcohol exposure programs the pituitary epithelium toward a mesenchymal stem cell‐like phenotype, contributing to the development of aggressive pituitary prolactinomas in both sexes.

Analysis of miR 16-5p, miR 143-3p and miR 423-5p in patients with invasive non-functioning pituitary adenomas and prolactinomas

Pre-treatment differentiation between non-functioning pituitary adenomas and prolactinomas based on serum prolactin levels

The study aimed to analyze hsa-miR-16-5p, hsa-miR-143-3p, hsa-miR-423-5p, hsa-miR-137-3p, hsa-miR-489-5p, hsa-miR-520-3p, hsa-miR-486-5p, and hsa-miR-200a-3p expression in the serum of patients with invasive non-functioning pituitary adenomas (NFPAs) and prolactinomas, as candidates for non-invasive biomarkers. The study included 62 patients with NFPAs and 18 with macroprolactinoma who qualified for transsphenoidal surgical resection. MicroRNAs were isolated from serum samples. The expression levels of hsa-miR-16-5p, hsa-miR-143-3p, hsa-miR-423-5p, hsa-miR-137-3p, hsa-miR-489-5p, hsa-miR-520-3p, hsa-miR-486-5p, and hsa-miR-200a-3p were determined using TaqMan MicroRNA assays. The statistical analyses were performed with MedCalc. The total concentration of microRNA was significantly lower in NFPAs than in the CG (p = 0.0419). ROC curve analysis showed that the cutoff point of miRNA lower than 10.73 predicted the PA (sensitivity = 70.0%; specificity = 57.7%; AUC = 0.629; p = 0.052). No correlation between selected miRNAs and tumor type was found: hsa-miR-143-3p (p = 0.4610), hsa-miR-16-5p (p = 0.8767), and hsa-miR-423-5p (p = 0.1459). miRNA expression also did not correlate with invasiveness (cavernous or sphenoid sinus invasion, optic chiasm compression). Although the total expression of microRNA was significantly lower in NFPAs, hsa-miR-16-5p, hsa-miR-143-3p, and hsa-miR-423-5p are not useful as non-invasive biomarkers in patients with invasive non-functioning pituitary adenomas and prolactinomas.

Concentrations of soluble alpha klotho (sαKL) are higher in active acromegaly compared with healthy controls. However, reference intervals based on large population-based samples are lacking, and the impact of many biological variables is unclear. Cross-sectional study. We measured sαKL concentrations in samples from an adult population (20-89 years, 435 males, 455 females). Associations with sex, age, body mass index, waist-hip-ratio, estimated glomerular filtration rate (eGFR), IGF-I and IGFBP 3, glucose-, lipid-, calcium- and liver-metabolism, fasting, and estrogen status were analyzed. Reference intervals were calculated using LMS quantile regression with a Box-Cox transformation to normality. We also analyzed sαKL in patients with non-functioning pituitary adenoma (NFPA, n = 18) and prolactinoma (n = 65). Across all ages, sαKL concentrations (pg/mL, median [interquartile ranges]) were slightly, but significantly higher in females compared with males (678 (537-859) vs. 651 (537-812), P = .01), suggesting an impact of estrogens. SαKL exhibited a weak negative correlation with age, and positive correlations with eGFR and IGF-I (P < .001 for both). Correlations to other biological factors including glucose, liver and calcium metabolism and duration of fasting were negligible (P > .05 for all). Compared with sαKL, IGF-I more often was correlated significantly to other biological variables. SαKL was not different in patients with NFPA, but slightly higher in patients with prolactinoma (P < .05). Our findings suggest sαKL is a stable GH-sensitive biomarker that may be less impacted by biological variables compared with IGF-I and IGFBP 3. Our reference intervals will facilitate the potential use of sαKL in GH-related diseases.

Peliosis hepatis (PH) is a rare disease with few clinical reports and complex etiology. However, there have been no reports of hyperprolactinemia (HPRL) leading to PH at present. This paper, through case reports, expands the understanding of the etiology of PH and the pathological damage effect of prolactin (PRL). The patient reported in this paper had jaundice, menstrual disorders, menopause, weight gain, and other symptoms. Laboratory examination found increased levels of PRL and transaminase in liver function, and imaging examination indicated pituitary tumor and PH. Comprehensive patient history and auxiliary examination, the clinical diagnosis was pituitary PRL tumor and PH. After treatment with bromocriptine, menstruation recovered and liver function returned to normal. In addition, the follow-up imaging examination indicated that pituitary tumors and PH lesions were shrinking, and clinical phenomena indicated that HPRL caused by pituitary prolactinoma was correlated with PH occurrence. Since there is no report of HPRL causing PH, the specific pathogenesis is unknown. This paper reviews the relevant literature and puts forward the theoretical consideration of the pathogenesis. Through this case, for clinically similar patients, it is warned that we need to consider the possibility of PH and further improve the examination, evaluation and treatment in time.

Abstract Disclosure: S.N. Polis: None. S. Nakhle: None. N.J. Vernetti: None. Prolactinomas are the most common type of secretory pituitary tumors. Symptoms occur due to hyperprolactinemia and compressive symptoms with larger tumors. The majority of the prolactinomas are benign adenomas, with up to 30-40% of them being invasive. Malignant prolactinomas are rare, counting only 0.2% of pituitary tumors with an average latency period of 4.7 years. We present a 70-year-old woman who was found to have asymptomatic mild hyperprolactinemia in 2009 with pituitary MRI that showed a 3 mm left pituitary adenoma. Treatment with cabergoline started three years later due to an increase in prolactin above 300 ng/ml. Annual pituitary MRI showed a stable mass. After four years of treatment, pituitary MRI showed an increase in pituitary adenoma size to 8 mm and prolactin level remained elevated above 300 ng/ml. The patient complained of facial and acral numbness and emotional outbursts, so cabergoline was changed to bromocriptine. A few months later, a decision was made to stop treatment as she was asymptomatic and prolactin levels remained stable with a stable adenoma on imaging. 18 months later, prolactin increased to 544 ng/ml and pituitary MRI showed an increase adenoma size to 14mm, contacting the chiasm, and cabergoline was restarted. The prolactin levels continued to climb after 5 months of treatment despite titrating the dose to 1 mg daily. The patient started to develop vision impairment and visual field testing confirmed a new central vision defect. The patient was eventually referred to neurosurgery and went for transsphenoidal surgery. Prolactin level dropped to 50 ng/ml post operatively. The pathology report showed Ki 67 10-20%. Cabergoline was restarted and the patient was enrolled in a clinical trial for temozolomide for 18 months. During that time, prolactin levels remained stable so treatment was discontinued. A year later, cabergoline was restarted as prolactin levels increased to 219 ng/ml and pituitary MRI showed an 8 mm sellar mass with optic chiasm compression. For the next year, multiple medical treatments including high dose cabergoline (1 mg daily) and temozolomide were attempted, which were intolerable due to side effects. Prolactin continued to climb (&amp;gt; 1700 ng/ml). Four years later, the patient went for a second transsphenoidal surgery. Surgical pathology revealed Ki67 20%. Prolactin levels dropped to 242 ng/ml, but a month later, went up again to over 600 ng/ml. Cabergoline was restarted with a plan for an open craniotomy and radiotherapy. Conclusion: We present this interesting case of pituitary prolactinoma that behaved as benign adenoma for over 10 years prior to invasion and showing aggressive behavior requiring multiple surgeries. This unusual presentation is worrisome for malignancy and prompting consideration for closer and longer follow up for prolactinomas, especially the ones resistant to medical treatment. Presentation: 6/2/2024

The pathological aspects of hyperprolactinemia have been well studied to date and primarily affect changes in the reproductive system. Regardless of the genesis of hyperprolactinemia, negative changes include, first of all, dysmenorrhea and hyperan drogenism. Changes in the mammary glands include galactorrhea, mastopathy, and the development of breast cancer. The pathological effects of hyperprolactinemia on other organs and systems, including the cardiovascular system, have been studied less. Few existing studies suggest that elevated prolactin levels can potentially affect cardiovas cular risks and provoke myocardial remodeling, arterial hypertension, hyperhomocys teinemia, and disorders of the plasma lipid profile. Menopausal women are particularly vulnerable in this regard, as the cardioprotective role of estrogens is significantly re duced during this period. In this article, we examined the effect of hyperprolactinemia on the formation of cardiovascular disorders in premenopausal women. The purpose of the study was to evaluate the effect of hyperprolactinemia on the genesis of cardiovascular pathology in premenopausal women. Materials and methods: three groups of premenopausal patients were examined. The patients of the first group (n=26) had previously been diagnosed with pituitary adenoma and were treated with cabergoline, maintaining the target prolactin level for at least two years. According to pituitary MRI, prolactinoma and elevated prolactin levels were de tected in the patients of the second group (n=21), but these patients did not take prolac tin-lowering therapy for various reasons. The third group consisted of the patients with idiopathic hyperprolactinemia who did not receive prolactin-lowering therapy (n=19). The patients of all three groups underwent general clinical examination, determination of the daily blood pressure profile, ECG, echocardiography, determination of the level of lipidogram, homocysteine, and other markers of cardiovascular risk. The results of the study showed that regardless of its genesis, pathological hyperprolactinemia influences the development of cardiovascular pathology in premenopausal women.

CASEObstructive hydrocephalus is a rare complication of pituitary prolactinomas, especially in females, where symptoms rarely go unnoticed. We present a 28-year-old Filipino female with a two-month history of frontotemporal headache, acutely worsening over three days. Cranial imaging showed a sellar-suprasellar mass with associated tonsillar herniation and obstructive hydrocephalus. Hyperprolactinemia was confirmed (prolactin: 8785.61 ng/mL), and cabergoline was initiated. Clinically, the patient’s headache resolved within 24 hours of the first dose, and repeat prolactin levels fell by 96% within the first month. Repeat imaging confirmed the resolution of the obstructive hydrocephalus within four weeks. Only nine previous cases of prolactinomas presenting with obstructive hydrocephalus have been described. Of these, only 3 were females. Most cases required surgical decompression. The resolution of the acute hydrocephalus within one month after initiation of treatment with cabergoline suggests that dopamine agonists, in select cases, may obviate the need for surgery, especially in resource-limited settings.

Abstract Disclosure: B. Alghamdi: None. L.A. Alobaid: None. M. Alswailem: None. E.O. Othman: None. M. Dababo: None. O. Alsagheir: None. A.S. Alzahrani: None. Pituitary adenomas (PA), renamed recently pituitary neuroendocrine neoplasms, are common and prolactinomas are the most common subtype of these tumors. The vast majority of PA are sporadic but they can also be due to germline (∼ 5%), mosaic (&amp;lt;1%) or somatic mutations (∼40%). PA with germline mutations might be part of a syndrome such as MEN1 or apparently sporadic, either due to de novo mutations or because of low penetrance of the underlying gene (e.g. AIP). Among the several genes that have been identified, CDH23 was reported to be associated with familial PA in a single study that included 12 families with PA (33% of them had CDH23 variants) and 125 sporadic PA (15 (12%) of them harbored CDH23 variants) compared to only 0.8% of 260 healthy controls. In this report, we describe a middle-aged woman who was incidentally found to have a huge macroprolactinoma with extensive invasion. Genetic testing revealed a novel germline CDH23 variant. Case report: A 53-year-old woman who with hypertension, diabetes and chronic renal insufficiency diagnosed 4 years before. She accidentally fell down on the back of her head. A CT and subsequent MRI scans of the head showed a huge mass extensively involving the Sella, suprasellar space, the cavernous sinuses and middle fossae. This mass extends inferiorly to the sphenoid and parasellar sinuses, nasopharynx, and appears at the nostrils. The patient reported chronic headaches, snoring and congested nose, and worsening hearing and vision over the last 4 years. She denied history of galactorrhea and her periods ceased 8 years before. She never got married and has no children. Her family history is negative for any pituitary or other tumors. The mass was initially thought to be a nasopharyngeal cancer. However, a bedside biopsy from the protruding mass in the right nostril revealed a pituitary tissue strongly positive for prolactin and weakly positive for growth hormone (GH). An undiluted serum prolactin level was 47 ug/l (3.4-24). After several dilutions for the hook effect, the level was 578,000 ug/l (3.4-24). IGF-1 253 ng/ml (93-245), random GH 4.7 ng/ml, TSH 1.9 mU/l (0.4-4.2), FT4 11.4 pmol/l (12-22), AM cortisol 235 nmol/l (159-620), ACTH 27.6 (5-60). Whole exome sequencing followed by Sanger sequencing revealed a novel variant in CDH23 (c.2621C&amp;gt;A, p.Ala874Asp). Several in silico analyses suggest that this variant is pathogenic and it is assigned variant of unknown significance (VUS) according to American College of Medical Genetics (ACMG) classification. It is not reported in EXAC and 1000G databases. All other known PA-associated genes and cancer-associated genes revealed no pathogenic variants. Conclusion: We report a massive prolactinoma, likely due to a novel CDH23 variant. This is the second report on the likely pathogenic role of this gene in PA. In the case reported here, it is associated with a huge and highly invasive pituitary macroadenoma. Presentation: Saturday, June 17, 2023

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1413579: Rathke Cleft Cyst Unveiling Incidental Prolactin Producing Adenoma