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Objective Testosterone concentrations, albeit rarely, may be in the normal range (>3.0 ng/mL) in men with a prolactin-secreting pituitary adenoma (PSPA-nt). The evolution of total, bioavailable testosterone, gonadotropin levels, and that of graded symptoms of testosterone deficiency (TD) are uncertain in these patients. Design Retrospective case-control longitudinal study at a tertiary referral center. Methods From 287 men, we selected 25 PSPA-nt men undergoing prolactin normalization (<20.0 ng/mL) during the follow-up. Graded symptoms of TD were investigated by structured interviews. Biochemical changes and TD symptoms were compared to those of a matched cohort of 61 men with pituitary neoplasms and normal testosterone levels (PA-nt). Results Baseline testosterone levels were similar between PSPA-nt and PA-nt subjects. The prevalence of specific and suggestive symptoms of TD was higher in PSPA-nt (20% and 68%) than in PAnt (3.3 and 29.5%; P =.02 and P =.0015, respectively). At the follow-up, total and bioavailable testosterone levels increased in PSPA-nt but not in PA-nt patients (Δ change: 1.28 ± 2.1 vs0.03 ± 1.5 ng/mL, + 0.33 ± 0.55 vs-0.26 ± 0.60 ng/mL; P =.0028 and P =.0088, respectively). LH and FSH levels also increased in PSPA-nt men (P <.05). Specific and suggestive, but not nonspecific symptoms of TD, improved only in PSPA-nt men (P <.05 for both). Baseline testosterone and LH were the strongest predictors of testosterone improvement in PSPA-nt patients. Conclusion Despite having normal testosterone levels at baseline, patients with PSPA-nt experience a relief of TD symptoms and an improvement of their pituitary-gonadal axis function following prolactin normalization, especially when baseline TT and LH levels are in the low-normal range. [ABSTRACT FROM AUTHOR]

Context Prolactinoma, the most common subtype of pituitary adenoma, is rare in children and adolescents. Clinical presentation and treatment outcomes of prolactinomas in this population have been evaluated insufficiently. Objective To summarize the clinical features, both medication and surgical outcomes of prolactinomas in children and adolescents in a large retrospective cohort from China. Methods A cohort of patients with prolactinomas aged ≤20 years at diagnosis between 2012 and 2021 in Peking Union Medical College Hospital were retrospectively analyzed. Results The cohort comprised 170 patients (115 females and 55 males, median age 16.6 years), with 20.0% (23/115) girls without menarche and 33.3% (18/54) boys in prepuberty. The median maximal diameter was 15.0 mm (61.2% macroadenomas and 4.6% giant adenomas), and the median baseline prolactin (PRL) level was 211.0 ng/mL. Larger sizes and higher PRL levels were observed in girls without menarche at diagnosis and in boys. Most girls presented with menstrual disturbance (86.7%), and boys were frequently bothered by headaches (42.6%), reduced height velocities (25.9%), and delayed puberty (18.2%). Dopamine agonists (DAs) were used as first-line treatment in 133 patients, and the resistance rate was 22.5% (25/111), independently associated with maximal tumor diameters (P =.035). Surgery was performed in 76 patients. Long-term surgical remission rates were 32.9% (25/76) overall, negatively associated with cavernous sinus invasion independently (P =.025), 59.4% (19/32) in noninvasive tumors (64.0% in 25 noninvasive macroadenomas), and 5.0% (1/20) in invasive tumors. Conclusion Pediatric prolactinomas exhibited more severe clinical characteristics in boys and in patients diagnosed during earlier stages of pubertal developments. Given the overall efficacy of PRL normalization by medication and considerable surgical remission rate in noninvasive tumors, DAs remain the first-line recommendation for prolactinomas in children and adolescents, while surgery might be viable for noninvasive tumors. [ABSTRACT FROM AUTHOR]

Objective: Prolactinoma can increase the risk of cardiovascular diseases (CVDs), such as arterial stiffness, atherosclerosis, dysrhythmia and heart failure. This study aimed to evaluate and compare muscle function, exercise capacity, physical activity (PA) level, CVD risk factor knowledge level, sleep quality, fatigue and quality of life between prolactinoma patients and healthy controls. Methods: Nineteen female patients with prolactinomas and 19 healthy women were included in this study. Quadriceps muscle strength (QMS) was measured using a hand dynamometer, and muscular endurance was evaluated via the squat test. The 6-minute walking test (6MWT) distance was also measured. CVD risk factor knowledge levels were evaluated with the Cardiovascular Diseases Risk Factors Knowledge Level Scale (CARRF-KL), PA levels were assessed with the International Physical Activity Questionnaire-short form (IPAQ), sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), fatigue was assessed with the Multidimensional Fatigue Rating Scale (MAF), and quality of life was assessed with the Short Form-36 questionnaire (SF-36). Results: Patients with prolactinomas had significantly lower 6MWT distances; CARRF-KL total scores; SF-36 general health and physical limitation scores; and higher IPAQ-sitting scores than did healthy controls (p < 0.05). Moreover, there were no significant differences between the groups in terms of QMS score; number of squats; severity of IPAQ score; severity, moderate, or total walking score; total PSQI score; or total MAF score (p > 0.05). Conclusions: Exercise capacity and quality of life are adversely affected, and sedentary behavior is observed in prolactinomas. Patients with prolactinomas have less knowledge about CVD risk factors than healthy individuals. CVD incidence and knowledge and functional capacity should be improved in patients with prolactinomas by the use of a multidisciplinary team for cardiac rehabilitation. Clinical trial registration: This study is part of a larger clinical trial registered on ClinicalTrials.gov prior to participant enrollment (NCT05236829). [ABSTRACT FROM AUTHOR]

Objective Methods Patients Results Conclusions The management of visual field damage in patients with macroprolactinomas is a major therapeutic challenge. We aimed to study the visual morbidity associated with macroprolactinoma and its outcomes following medical and surgical treatment. We aimed to identify predictors of visual recovery.We retrospectively reviewed patient's data including clinical presentation, serial pituitary magnetic resonance imaging, laboratory tests, visual symptoms and neuro‐ophthalmologic examination, visual field tests and optical coherence tomography tests. The main outcome was complete visual field recovery. Descriptive analyses were conducted. Predictors of visual recovery were investigated.The study cohort included 150 patients with macroprolactinoma [median follow‐up, 6.0 years (interquartile range (IQR) 2.9–10.6)].At diagnosis, visual field defects were evident in 40 patients (26.7%). At the end of follow‐up, 24 out of 39 available visual field tests (61.5%) exhibited complete recovery. Patients that achieved complete visual recovery had smaller macroadenomas at diagnosis [30.5 mm (15.0–80.0) vs. 42.0 mm (30.0–85.0), p < .01], lower baseline serum prolactin levels [1414 mcg/L (489–3586) vs. 4119 mcg/L (2715–6315), p < .01], lower rates of central hypogonadism (78.3% vs. 93.3%, p = .05) and central hypothyroidism (20.8% vs. 53.3%, p = .04), lower rates of compressive optic neuropathy (35.3% vs. 87.5%, p = .02) and a better visual acuity (better than 6/8 in both eyes, 93.7% vs. 28.6%, p < .01).In our cohort of 150 patients with macroprolactinoma, 40 patients (26.7%) presented with visual field defects, of which 61.5% achieved complete visual recovery with treatment. Patients that achieved complete visual recovery presented with smaller macroadenomas, lower serum prolactin levels, lower rates of central hypogonadism and central hypothyroidism, lower rates of compressive optic neuropathy and better visual acuity. [ABSTRACT FROM AUTHOR]

This article discusses the case of a transgender woman who successfully induced lactation without the use of galactagogues. The article highlights the benefits of breastfeeding for both mother and child and acknowledges the limited research on lactation induction in the LGBTQ community. The case report describes the patient's protocol, which involved increased estrogen and progesterone levels, physical nipple stimulation, and reduced hormone dosing before delivery. The patient was able to produce milk, although she ultimately decided not to breastfeed due to external stressors. The article emphasizes the importance of patient-centered care and the potential overlap between nipple stimulation and galactagogues in lactation induction. [Extracted from the article]

Pituitary adenomas (PAs) are the third most common brain tumors in adults right after meningiomas and gliomas. Taking into account their hormonal activity in vivo, they can be divided in functioning PAs, which secrete hormones, and nonfunctioning pituitary adenomas (NFPAs), which are not associated with increased hormone secretion. We present the case of a man diagnosed with pituitary apoplexy. A transsphenoidal surgery was performed with subtotal removal of the mass. Pituitary hormones were measured before and after the procedure on several occasions, showing always normal PRL values, so he was diagnosed with a clinically NFPA. Two years later, the patient noticed a visual deficit. A new magnetic resonance imaging study was performed, showing adenomatous recurrence, and the patient underwent a new surgery. After this, hormonal evaluation revealed high levels of PRL on several occasions. After treatment with cabergoline was started, PRL levels normalized, the visual deficit improved, and there was a slight adenoma reduction. This case report represents an exception to the paradigm that in the presence of a macroadenoma and normal PRL levels (avoiding the "hook effect"), a prolactinoma can be discarded. Moreover, it stresses the importance of comprehensive, regular, and lifelong surveillance of patients with NFPAs and the close monitoring of serum PRL. [ABSTRACT FROM AUTHOR]

McCune-Albright syndrome (MAS) is a rare genetic, non-inheritable disease and is characterized by fibrous dysplasia, hyperendocrinism, and café-au-lait macules. Pituitary adenomas could be concurrent with this syndrome but clinicopathological features and the surgical management of such disorders is unclear. We retrospectively reviewed ten MAS-associated pituitary adenoma patients with follow-up in Beijing Tiantan Hospital and analyzed their clinicohistological data, surgical strategies, neuro-imaging, genetic mutations, and prognosis. Moreover, a critical review of the English language literature was also conducted. All of the ten MAS-associated adenoma patients underwent surgeries to remove the tumor (nine transsphenoidal approaches and one transcranial approach). None of these patients had a decompression of the optic canal. Notably, the growth hormone (GH), prolactin (PRL), and IGF-1 level had a significant reduction after the resection of the tumor while vision improvement was observed in most patients (6/7) with visual deficits. No tumor recurrence was observed during the follow-up from 16 to 150 months. The pathological examination showed a moderate Ki-67 LI (mean 1.19%, range from 0.1% to 3.3%) and the positive staining of Gsα and PKA C-beta. GNAS gene mutation (R201C) was detected in one patient. Hormone excess (including GH and PRL) could be significantly reduced and the visual deficits are greatly improved after the surgery without the decompression of the optic canal. In addition, MAS-associated pituitary adenomas have a moderate expression of Ki-67 and positive expression of Gsα and PKA C-beta, indicating a mildly proliferative nature of these tumors and the possible linking between MAS and adenomas. [ABSTRACT FROM AUTHOR]

Moyamoya disease is a rare chronic progressive cerebrovascular disease. The etiology of moyamoya disease has not been established yet. If an underlying cause is detected, moyamoya disease is called moyamoya syndrome. A 27-year-old right-handed male was admitted to an external medical center with recurrent severe headaches, vomiting, and seizures. He was diagnosed with prolactinoma as a result of cranial magnetic resonance imaging and blood tests. After three months, he presented again with headache and left-sided weakness affecting both his arm and leg. Head and neck computed tomography angiography showed critical stenosis in the right distal internal carotid artery (ICA), in the right supraclinoid ICA, in the left supraclinoid ICA, and occlusion in the right ICA and middle cerebral artery. Digital subtraction angiography was performed following a preliminary diagnosis of Behçet's disease due to HLA B51 positivity. However, the results did not support a diagnosis of neuro-Behçet's but were instead indicative of moyamoya disease. This is the third case in which prolactinoma and moyamoya disease occur together. Moyamoya disease is a very rare chronic disease that mostly affects the cranial vessels. Patients can apply with very different complaints that may mimic other diseases. [ABSTRACT FROM AUTHOR]

Context Prolactin (PRL) is a highly versatile, multifunctional hormone synthesized and secreted by lactotroph cells of the anterior pituitary. Its metabolic role has been extensively studied even in normoprolactinemic populations. Recently, a wealth of observational data have outlined the potential prognostic value of PRL in various clinical settings. Objective This systematic review aims to systematically evaluate and quantitatively synthesize the association between serum PRL levels and risk of mortality in adults without prolactinoma. Methods A systematic literature search was conducted up to June 10, 2023, to identify studies reporting the association of serum PRL levels with clinical outcomes of adults without prolactinoma. A random-effects meta-analysis was conducted to quantify the adjusted hazard ratios [(a)HRs] for all-cause and cardiovascular death (CVD) during follow-up. Results Twenty-eight studies were deemed eligible reporting the outcomes of adults without prolactinoma, in whom serum PRL levels were measured for risk-stratification. Fourteen studies reported appropriate data for meta-analysis encompassing a total of 23 596 individuals. Each unit of PRL increase was independently associated with increased risk of all-cause (pooled aHR = 1.17 [1.08-1.27]; I2 = 48%) and CV mortality (pooled aHR = 1.54 [1.14-2.09]; I2 = 89%). Individuals belonging to the highest PRL category had significantly higher risk for all-cause (pooled aHR = 1.81 [1.43-2.30]; I 2 = 65%) and CV (pooled aHR = 1.59 [1.04-2.42]; I 2 = 82%) mortality compared to their lowest-PRL category counterparts. The association between PRL levels and in-hospital death did not reach statistical significance. Conclusion PRL levels seem to be an independent predictor for mortality. Further validation is warranted before its role as a risk-stratification tool can be delineated in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Non-functioning pituitary adenomas (NFPAs) are often associated with hyperprolactinemia, which is known as the "stalk effect". However, the relationships between hyperprolactinemia and the radiographic characteristics of the tumor that affects the pituitary stalk have not been well characterized. We aimed to identify the differences in the clinical and radiographic characteristics of patients with NFPA, with and without hyperprolactinemia. Methods: We enrolled 107 patients with NFPA and allocated them to hyperprolactinemia and non-hyperprolactinemia groups using two different cut-off values: (1) the upper limit of the normal reference range, adjusted for sex and menopausal status, and (2) the upper quartile across the cohort, and compared their clinical and radiographic characteristics. These analyses were conducted to clarify the relationship between the "stalk effect" and the postoperative change in antidiuretic hormone secretion. Results: The specific radiographic characteristics of the patients included the presence of a cystic or hemorrhagic tumor and the presence of pituitary stalk deviation, which were more frequent in the patients with hyperprolactinemia. Interestingly, the incidence of postoperative transient diabetes insipidus was statistically significantly higher in the hyperprolactinemia group (≥40 ng/mL) and in the group with radiologic evidence of stalk deviation, which were shown to be independent risk factors on multivariate analysis. Conclusion: The presence of a "stalk effect" was associated with a higher risk of postoperative transient diabetes insipidus, reflecting perioperative pituitary stalk dysfunction following NFPA surgery, especially in patients with serum prolactin concentrations ≥40 ng/mL and radiologic evidence of stalk deviation. [ABSTRACT FROM AUTHOR]

Background and Objectives: Prolactinomas are the most common pituitary adenomas, comprising 30–50% of such tumors. These adenomas cause hyperprolactinemia, leading to decreased fertility, reduced energy and libido, and galactorrhea. Diagnosing and treating prolactinomas in adolescents present unique challenges, as symptoms may be confused with age-related developmental variations. This case report explores the outcomes of early surgical intervention in an adolescent with a prolactinoma. Materials and Methods: A 14-year-old female presented delayed menarche and absent pubertal development. Initial evaluation revealed hyperprolactinemia (228.37 ng/mL) with normal estradiol levels. Initial management through observation was adopted, but persistent amenorrhea and severe headaches prompted further investigation. Magnetic resonance imaging revealed a cystic pituitary mass with apoplexy. Due to concerns regarding delayed puberty and the need for rapid normalization of prolactin levels, the patient underwent transsphenoidal surgery. Results: After operation, prolactin levels normalized, menarche occurred within three months, and secondary sexual characteristics developed within eight months. Pathology confirmed a pituitary adenoma with a high Ki-67 index (15%). Conclusions: Early surgical intervention for prolactinomas in adolescents can achieve successful biochemical remission and resolution of endocrine symptoms. Adolescents, particularly those with a high Ki-67 index and potential resistance to dopamine agonists, may benefit from prompt surgical management, resulting in improved clinical outcomes and complete tumor resection. [ABSTRACT FROM AUTHOR]

Cardiovascular comorbidities owing to hormonal excess or deficiency are the main cause of mortality in patients with pituitary disorders. In patients with Cushing's Disease, there is an increased prevalence of cardiovascular diseases and/or risk factors including visceral obesity, insulin resistance, atherosclerosis, arterial hypertension, dyslipidaemia, hypercoagulability as well as structural and functional changes in the heart, like cardiac hypertrophy and left ventricle (LV) dysfunction. Notably, these demonstrate limited reversibility even after remission. Furthermore, patients with acromegaly may manifest insulin resistance but also structural and functional heart changes, also known as "acromegalic cardiomyopathy". Patients with prolactinomas demonstrate an aggravation of metabolic parameters, obesity, dysregulation of glucose and lipid metabolism as well as endothelial dysfunction. Hypopituitarism and conventional hormonal replacement therapy may also contribute to an unhealthy metabolic status, which promotes atherosclerosis and may lead to premature mortality. This review discusses the literature on cardiovascular risk in patients with pituitary disorders to increase physician awareness regarding this aspect of management in patients with pituitary disorders. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Large and giant pituitary adenomas (defined as tumors of maximal diameter ≥ 3–3.9 cm and ≥ 4 cm, respectively) present considerable surgical challenges regarding the extent of resection and perioperative morbidity. Endoscopic endonasal resection is considered the most effective treatment for pituitary adenomas. It allows for better visualization, maneuverability, and access to distant and lateral tumor compartments, ultimately enhancing the extent of resection. This article evaluates our initial experience with endoscopic endonasal resection of large and giant pituitary adenomas. The clinical outcomes, perioperative complications, and extent of tumor resection would be specifically addressed. Patients and methods: The primary goal of surgery was to decompress the optic pathways, and the secondary goals were to achieve maximal safe resection and hormonal control in hormone-secreting adenomas. The degree of tumor resection was classified as gross-total resection (100%), near-total resection (90–100%), subtotal resection (70–90%), and partial resection (< 70%). Results: 42 patients were included in this study. A good visual outcome achieved with 80% improvement in visual symptoms. Gross-total resection (GTR) was achieved in 19 patients (45.2%), near-total resection (NTR) was achieved in 12 patients (28.6%), subtotal resection (STR) in 6 patients (14.3%), and partial resection in the remaining 5 patients (11.9%). Subgroup analysis revealed that GTR, NTR rates were higher in large, compared to giant tumors. GTR, NTR rates of large adenomas were 59.3%, and 29.6%, compared to 20%, and 26.7% in giant adenomas respectively (p-value: 0.01428). Surgical complications were observed in 19 patients (45.2%) with CSF leakage being the most common complication (11 patients, 26.2%). Post-operative diabetes insipidus was observed in 5 patients (11.9%), major vascular injury in one case (2.4%), transient post-op 6th nerve palsy observed in 3 patients (7.1%), while two patients (4.8%) presented with post-operative paranasal sinuses infection. Conclusions: Endoscopic endonasal transsphenoidal resection of large and giant pituitary adenomas is a safe and efficient procedure. Large adenomas (3–3.9 cm) have excellent resection rates and lower complications than giant adenomas (≥ 4 cm), which may require extending our approach to achieve more tumor resection rates in the future. However, only adequate resection of these giant adenomas can be enough to achieve the main surgical goals of visual improvement, hormonal control, and decompression of surrounding structures. [ABSTRACT FROM AUTHOR]

Pituitary adenomas are very common representing 18.1% of all brain tumors and are the second most common brain pathology. Transsphenoidal surgery is the mainstay of treatment for all pituitary adenomas except for prolactinomas which are primarily treated medically with dopamine agonists. A thorough endocrine evaluation of pituitary adenoma preoperatively is crucial to identify hormonal compromise caused by the large sellar mass, identifying prolactin‐producing tumors and comorbidities associated with Cushing and acromegaly to improve patient care and outcome. Transsphenoidal surgery is relatively safe in the hands of experienced surgeons, but still carries a substantial risk of causing hypopituitarism that required close follow‐up in the immediate postoperative period to decrease mortality. A multidisciplinary team approach with endocrinologists, ophthalmologists, and neurosurgeons is the cornerstone in the perioperative management of pituitary adenomas. [ABSTRACT FROM AUTHOR]

Introduction: Lactotroph pituitary neuroendocrine tumors (PitNETs) are common pituitary tumors, but their underlying molecular mechanisms remain unclear. This study aimed to investigate the transcriptomic landscape of lactotroph PitNETs and identify potential molecular mechanisms and therapeutic targets through RNA sequencing and ingenuity pathway analysis (IPA). Methods: Lactotroph PitNET tissues from five surgical cases without dopamine agonist treatment underwent RNA sequencing. Normal pituitary tissues from 3 patients served as controls. Differentially expressed genes (DEGs) were identified, and the functional pathways and gene networks were explored by IPA. Results: Transcriptome analysis revealed that lactotroph PitNETs had gene expression patterns that were distinct from normal pituitary tissues. We identified 1,172 upregulated DEGs, including nine long intergenic noncoding RNAs (lincRNAs) belonging to the top 30 DEGs. IPA of the upregulated DEGs showed that the estrogen receptor signaling, oxidative phosphorylation signaling, and EIF signaling were activated. In gene network analysis, key upstream regulators, such as EGR1, PRKACA, PITX2, CREB1, and JUND, may play critical roles in lactotroph PitNETs. Conclusion: This study provides a comprehensive transcriptomic profile of lactotroph PitNETs and highlights the potential involvement of lincRNAs and specific signaling pathways in tumor pathogenesis. The identified upstream regulators may be potential therapeutic targets for future investigations. [ABSTRACT FROM AUTHOR]

A recent Pituitary Society consensus statement provided clinical recommendations for diagnosing and managing prolactin-secreting pituitary adenomas, known as prolactinomas. Prolactinomas are rare, usually benign tumours of the anterior pituitary gland that result in excessive prolactin production, or hyperprolactinemia. Despite being non-life- -threatening, patients often prompt medical attention due to symptoms stemming from elevated prolactin levels, such as reproductive and sexual dysfunction, e.g. menstrual irregularities, galactorrhoea, infertility, or from mass effects like headaches, cranial nerve palsies, and vision problems. Laboratory testing showing hyperprolactinemia and low sex hormone levels is used for diagnosis. Unlike other pituitary tumours, the primary treatment for prolactinomas is typically pharmacological therapy with dopamine agonists. However, for patients with smaller tumours (microprolactinomas) or well-circumscribed larger tumours (macroprolactinomas), surgery may be considered the first-line option. It is a surprising shift in the therapeutic strategy. For patients resistant to dopamine agonists, alternative strategies include switching medications, increasing dosages, or pursuing neurosurgery or radiotherapy. The key treatment goals are to normalize prolactin levels, restore reproductive and sexual function, and reduce tumour size. This review aimed to provide clinicians with an up-to-date overview of diagnostics and treatment options for patients with prolactin- -secreting pituitary adenomas, as well as highlight the potential diagnostic challenges and complexity of treatment. [ABSTRACT FROM AUTHOR]

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Background: Men with macroprolactinoma can present persistent hypogonadism despite normoprolactinemia achieved with clinical and/or neurosurgical treatment. Usually, testosterone replacement therapy is indicated. Nevertheless, although off-label, clomiphene citrate (CC), a selective estrogen receptor modulator, has also been used, mainly when fertility is an issue. The aim of this study is to evaluate the effectiveness of CC in recovering the gonadal axis in men with macroprolactinoma, with or without hyperprolactinemia, and evaluate its safety as a long-term therapy. Methods: This is a retrospective study including 10 men with macroprolactinoma on cabergoline treatment and persistent hypogonadism. All patients received initially 50 mg/d of CC. Results: The median age at diagnosis of prolactinomas was 34 (range, 26–60) years old. All patients were treated with cabergoline at a median maximum dose of 2 (1–7) mg/week, with a median time of treatment of 8.5 (2–15) years. Prolactin was still above the normal range when CC was introduced only in two patients. The mean duration of CC therapy was 3.2 (±2.8) years. Prolactin levels maintained stable (p = 0.252) and testosterone increased (p = 0.027) significantly on CC therapy. Tumor size remained stable. Eight patients (80%) maintained testosterone above 300 ng/dL and were classified as responders. Three responders succeeded in using a lower dose of CC and one of them completed withdrawal CC and maintained eugonadism. There were no side effects or safety concerns reported. Conclusion: CC should be seen as a safe treatment option for men with macroprolactinoma and persistent hypogonadism. [ABSTRACT FROM AUTHOR]

Moyamoya disease is a rare chronic progressive cerebrovascular disease. The etiology of moyamoya disease has not been established yet. If an underlying cause is detected, moyamoya disease is called moyamoya syndrome. A 27-year-old right-handed male was admitted to an external medical center with recurrent severe headaches, vomiting, and seizures. He was diagnosed with prolactinoma as a result of cranial magnetic resonance imaging and blood tests. After three months, he presented again with headache and left-sided weakness affecting both his arm and leg. Head and neck computed tomography angiography showed critical stenosis in the right distal internal carotid artery (ICA), in the right supraclinoid ICA, in the left supraclinoid ICA, and occlusion in the right ICA and middle cerebral artery. Digital subtraction angiography was performed following a preliminary diagnosis of Behçet’s disease due to HLA B51 positivity. However, the results did not support a diagnosis of neuro-Behçet’s but were instead indicative of moyamoya disease. This is the third case in which prolactinoma and moyamoya disease occur together. Moyamoya disease is a very rare chronic disease that mostly affects the cranial vessels. Patients can apply with very different complaints that may mimic other diseases.

Abstract Purpose An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index. Methods We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55). Results IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04). Conclusions Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies.

Purpose: An increase of IGF-1 has been reported during therapy with dopamine agonists (DA) for prolactinomas; in such cases a correct diagnosis is pivotal to avoid an unnecessary reduction or withdrawal of DA, which are needed to maintain normal prolactin levels. This study was aimed to measure IGF-1 levels, at baseline and during follow-up, in a cohort of patients with prolactinoma, treated with cabergoline, stratified by body mass index. Methods: We retrospectively enrolled 35 patients (15 F/20 M; age m ± SD, years: 43.4 ± 13.7) with prolactinoma (21 microadenomas and 14 macroadenomas) who were followed-up at the Endocrinology Unit, in Siena, and with available pituitary hormone assessment at baseline and during follow-up (m ± SD, years: 2.74 ± 0.55). Results: IGF-1 increased in the whole cohort, but remaining within normal range, except two patients, in whom acromegaly was ruled out with oral glucose tolerance test. After dividing patients by weight, this trend was confirmed only in subjects with overweight and obesity (OV/OB) (p = 0.04). Interestingly, the reduction of prolactin levels was significantly greater in the OV/OB compared to normal-weight patients (median decrease of 97.5% versus 88.2%, p = 0.04). Conclusions: Since DA and normalization of prolactin are known to improve insulin sensitivity, we speculated they have favored the increase of IGF-1 in OV/OB. Our results should be confirmed and the hypothesis proven by further studies. [ABSTRACT FROM AUTHOR]

The objective of this study is to conduct a bibliometric analysis of research trends in hyperprolactinemia from 2011 to 2023. This analysis aims to provide researchers with insights into the current hotspots and frontiers related to hyperprolactinemia. It is worth noting that there are currently no existing reports on bibliometric analyses of hyperprolactinemia. The Social Science Citation Index (SSCI) and Science Citation Index Expanded (SCIE) databases of the Web of Science Core Collection were systematically searched for “articles” and “review articles” related to the topic of hyperprolactinemia from 2011 to 2023. VOSviewer was employed to conduct bibliometric analysis, aiming to analyze the research trends in hyperprolactinemia over the past 13 years. A total of 1865 eligible articles were retrieved, with contributions from 9544 scholars representing 83 countries in the field of research. The United States had the highest number of publications, followed by China. The keywords were categorized into six clusters: (1) etiology of hyperprolactinemia and other related endocrine and metabolic diseases. (2) Hyperprolactinemia and mental illness. (3) Diagnosis and management of hyperprolactinemia. (4) Treatment of hyperprolactinemia and prolactinoma. (5) Detection of macroprolactin and macroprolactinemia. (6) Symptoms of male hyperprolactinemia. Over the past 13 years, there has been a consistent and slightly increasing trend in the number of research papers focusing on hyperprolactinemia. The primary areas of research focus are centered around the diagnosis and treatment of hyperprolactinemia caused by antipsychotic drugs or prolactinoma. [ABSTRACT FROM AUTHOR]

Background: An ACTH-secreting pituitary adenoma is the most common cause of excessive endogenous glucocorticoid production resulting in Cushing's Syndrome. A multidisciplinary approach is paramount. Selective adenomectomy is the treatment of choice. Method: Endoscopic transnasal transsphenoidal approach to the tumour, along with techniques for resection, are demonstrated. Conclusion: Endoscopic transsphenoidal approaches with its magnified view of the pituitary gland allows precise microsurgical dissection during selective adenomectomy. This technique increases the possibility of proving a gross total resection, leading to clinical and biochemical cure in these patients. [ABSTRACT FROM AUTHOR]

Introduction: Impulse control disorders (ICDs) are defined as excessive and repetitive behaviors that may affect Parkinson's disease (PD) patients exposed to dopamine agonists. Current data on ICDs in patients with early-onset Parkinson's disease (EOPD) is lacking. In this study we aim to assess the frequency of use of dopamine agonists, the prevalence of ICDs, and to explore potential factors associated with their development in patients with EOPD. Methods: We used the Mayo Clinic Data Explorer system to investigate a population-based cohort of EOPD patients between 1990 and 2022 at Mayo Clinic, Rochester, MN. We used ICD coding for parkinsonism; then, we reviewed all the clinical records and included only those patients with a clinical diagnosis of PD with symptoms onset at or before the age of 50, and who developed ICDs after using therapeutic doses of dopamine agonists. Results: A total of 831 (513 males and 318 females) patients with EOPD were included with a median age at symptom onset of 42 years of age (CI: 37-46). Dopamine agonists were used in 49.7% of all patients; of these, only 14.5% developed symptoms of one or more ICDs. Hypersexuality was the most commonly observed ICD (38.3%), and the only one having a statistically significant male predominance (p = 0.011). Conclusion: ICDs are common in EOPD, particularly when associated with the use of dopamine agonists. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are known as antigen‐presenting cells that are capable of regulating immune responses. DCs and T cells can interact mutually to induce antigen‐specific T‐cell responses. Cabergoline, which is a dopamine (DA) receptor agonist, seems to implement anti‐inflammatory properties in the immune system, and therefore in the present study the impact of a DA receptor agonist cabergoline on the monocyte‐derived DCs (moDCs) was assessed. Immature moDCs were treated with lipopolysaccharide to produce mature DCs (mDCs). The expression of DCs' related surface markers namely: CD11c, HLA‐DR, and CD86 was measured by utilizing of flow cytometry. Real‐time PCR was the technique of choice to determine the levels at which diverse inflammatory and anti‐inflammatory factors in cabergoline‐treated and control mDC groups were expressed. DCs treated with cabergoline displayed a significant decrease in CD86 and HLA‐DR expression, markers linked to maturation and antigen presentation, respectively. In addition, the cabergoline‐mDC group showed a considerable decline in terms of the levels at which IL‐10, TGF‐β, and IDO genes were expressed, and an increase in the expression of TNF‐α and IL‐12 in comparison to the mDC control group. Our findings revealed that cabergoline as an immunomodulatory agent can relatively shift DCs into an immunogenic state, and there is a requirement for further investigations to evaluate the effects of cabergoline‐treated DCs on the T cell responses in vitro, and also in various diseases including cancer in animal models. Significance statement: Cabergoline‐mediated dopamine receptor provoking in the monocyte‐derived dendritic cells (DCs) significantly decreased CD86 and HLA‐DR expression, markers linked to maturation and antigen presentation, respectively. Furthermore, it could downregulate the expression of IL‐10, TGF‐β, and IDO genes, and upregulate the expression of TNF‐α and IL‐12 genes. Our findings revealed that cabergoline as an immunomodulatory agent can shift DCs into a partially immunogenic state. [ABSTRACT FROM AUTHOR]

Background: Prolactin (PRL) is a pituitary hormone promoting lactation in response to the suckling reflex. Beyond its well‐known effects, novel tissue‐specific and metabolic functions of PRL are emerging. Aims: To dissect PRL as a critical mediator of whole‐body gluco‐insulinemic sensitivity. Methods: PubMed‐based search with the following terms 'prolactin', 'glucose metabolism', 'type 2 diabetes mellitus', 'type 1 diabetes mellitus', 'gestational diabetes mellitus' was performed. Discussion: The identification of the PRL‐glucose metabolism network poses the basis for unprecedented avenues of research in the pathogenesis of diabetes mellitus type 1 or 2, as well as of gestational diabetes. In this regard, it is of timely relevance to define properly the homeostatic PRL serum levels since glucose metabolism could be influenced by the circulating amount of the hormone. Results: This review underscores the basic mechanisms of regulation of pancreatic β‐cell functions by PRL and provides a revision of articles which have investigated the connection between PRL unbalancing and diabetes mellitus. Future studies are needed to elucidate the burden and the role of PRL in the regulation of glucose metabolism and determine the specific PRL threshold that may impact the management of diabetes. Conclusion: A careful evaluation and context‐driven interpretation of PRL levels (e.g., pregnancy, PRL‐secreting pituitary adenomas, drug‐related hyper‐ and hypoprolactinemia) could be critical for the correct screening and management of glucometabolic disorders, such as type 1 or 2 as well as gestational diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background The coexistence of two histologically distinct neoplasms in the same area without histological admixture or an intermediate cell population zone represents a rare tumor type called collision tumor. Collision tumor of pituitary adenoma and meningioma has been reported years later following irradiation to pituitary adenoma. However, collision tumor of pituitary adenoma and meningioma in absence of irradiation therapy is extremely uncommon. Case Description We report an unusual case of collision tumor involving diaphragma sella meningioma and pituitary adenoma in a 50-year-old lady without prior radiation therapy. She presented with visual blurring and impaired field of vision. Her preoperative magnetic resonance imaging (MRI) was suggestive of pituitary adenoma. Total excision of the lesion was performed through endoscopic transsphenoidal route. Histological diagnosis was consistent with collision tumor of pituitary adenoma and meningioma. Conclusion Collision tumor comprising of nonfunctioning pituitary adenoma and meningioma is extremely rare. Preoperative MRI may not always be able to distinguish these histologically distinct neoplasms. Hence, histopathological examination is necessary to establish the diagnosis. Endoscopic transsphenoidal approach may suffice in excision of these collision tumors. Close follow-up is necessary to detect tumor recurrence. Though the association of these tumors can be coincidental, casual relationship between the occurrence of collision tumors cannot be totally excluded. [ABSTRACT FROM AUTHOR]

The new World Health Organization nomenclature of pituitary tumors was introduced in the year 2022 after much deliberation. This nomenclature clearly demarcates the anterior lobe (adenohypophyseal), posterior lobe (neurohypophyseal), and hypothalamic tumors. There is also focus on other tumors arising in the sellar region. The nomenclature has also advocated the routine use of immunohistochemistry in describing the pituitary transcription factors that plays a fundamental role in distinguishing the cell lineage of these tumors. However, the nomenclature is complex in understanding due to inclusion of pathological correlates like transcription factors, hormones, biomarkers, and various controversies that have emerged regarding the renaming of pituitary adenomas (PA) as PiTNETs ("Pituitary Neuroendocrine tumors") because majority of the adenomas are benign and have rare metastatic behavior while classifying them as PiTNETs will create unnecessary misinterpretation of these as aggressive tumors that will lead to apprehension among the patients. The new classification gives deeper insight into the histological picture of the various pituitary tumors but other than contributing to the follow-up strategy and postsurgery management, this classification does not add anything new that could be advantageous for the neurosurgeons in clinical practice and decision making, especially in deciding the plan of action for surgery. Hence, there is need of a more comprehensive, integrated, neuroradiological-based classification with more emphasis on the invasiveness of these tumors that would assist the neurosurgeons in planning the treatment strategy and managing patients of pituitary tumors. [ABSTRACT FROM AUTHOR]

Objective Unravel the potential mechanism(s) of the on- and off-target actions of dopamine agonist therapy in both human prolactinoma tumors and neighboring stromal and immune cells. Design and Methods Five surgically resected prolactinomas (PRLomas) from 3 cabergoline (CBG)-treated patients and 2 treatment-naive patients were analyzed by using single-cell RNA sequencing (scRNA-seq) to compare the cellular composition and transcriptional landscape. Results Six major cell populations, namely tumor (88.2%), immune (5.6%), stromal (4.9%), progenitor cells (0.6%), proliferating cells (0.4%), and erythrocytes (0.2%), were observed. Tumor cells from CBG-treated patients expressed lower levels of genes that regulated hormone secretion, such as SCG2, VGF, TIMP1, NNAT, and CALD1, consistent with the inhibitory effects of CBG on hormone processing and secretion. Interestingly, we also observed an increased number of CD8+ T cells in the CBG-treated tissues. These cytotoxic CD8+ T cells expressed killing granule components such as perforin and the granzymes GZMB, GNLY, and KLRD1 as well as the inflammatory cytokine CCL5. Immune cell activation of these CD8+ T cells was further analyzed in a compartment-specific manner, and increased CD25 (IL2R) expression was noted in the CD8+ T cells from the CBG-treated samples. Additionally, and confirming prior reports, we noted a higher stromal cell population in the CBG-treated samples. Conclusions Our scRNA-seq studies revealed key differences in the transcriptomic features of CBG-treated and CBG-untreated PRLomas in both tumor and microenvironment cellular constituents, and for the first time, describe the previously unknown activation of CD8+ T cells following CBG treatment, which may play a role in the tumoricidal actions of CBG. [ABSTRACT FROM AUTHOR]

Background Most pituitary adenomas (PAs), also termed pituitary neuroendocrine tumors, are benign in nature and can be treated effectively by surgical resection, medical treatment, and in special cases by radiotherapy. However, invasive growth can be an important feature of a more aggressive behavior and adverse prognosis. The extension of PAs into the cavernous sinus can be categorized according to the Knosp criteria on magnetic resonance imaging (MRI). Comparative analyses of MRI features and intraoperative findings of invasive growth regarding different clinical factors are still scarce. Materials and Methods We performed a retrospective single-center analysis of 764 PAs that were surgically treated between October 2004 and April 2018. Invasive growth was assessed according to the surgical reports and preoperative MRI (Knosp criteria). Clinical data, such as patient age at diagnosis and gender, histopathological adenoma type, and extent of resection, were collected. Results Invasive features on MRI were seen in 24.4% (Knosp grades 3A-4, 186/764) of the cases. Intraoperatively, invasion was present in 42.4% (324/764). Complete resection was achieved in 80.0% of adenomas and subtotal resection, in 20.1%. By multivariate analysis, invasion according to intraoperative findings was associated with the sparsely granulated corticotroph (SGCA, P =.0026) and sparsely granulated somatotroph (SGSA, P =.0103) adenoma type as well as age (P =.0287). Radiographic invasion according to Knosp grades 3A-4 correlated with age (P =.0098), SGCAs (P =.0005), SGSAs (P =.0351), and gonadotroph adenomas (P =.0478). Both criteria of invasion correlated with subtotal resection (P =.0001, respectively). Conclusions Both intraoperative and radiographic signs of invasive growth are high-risk lesions for incomplete extent of resection and occur more frequently in older patients. A particularly high prevalence of invasion can be found in the SGCA and SGSA types. Cavernous sinus invasion is also more common in gonadotroph adenomas. Usage of the Knosp classification is a valuable preoperative estimation tool. [ABSTRACT FROM AUTHOR]

Introduction: Headache is one of the essential symptoms of pituitary adenoma associated with the tumor and the patient’s characteristics. The pattern of adenoma-related headaches varies widely and can significantly impact the patient’s quality of life. Objectives: We aimed to investigate the severity and pattern of headaches in patients with pituitary adenoma in Iran. Patients and Methods: In this cross-sectional study, we investigated 109 patients with an initial complement of headaches. The diagnosis of pituitary adenoma was confirmed. Patients’ demographic characteristics [e.g., gender, body mass index (BMI), and age] and tumor characteristics (e.g., subtype of tumor and size of tumor) were collected by interview, clinical examination, and imaging. We measured the severity of the headache using Headache Impact Test-6 (HIT-6) questionnaire version 1.1. Results: In our study, the most common subtype of pituitary adenoma was prolactinoma, followed by nonfunctional growth hormone (GH)-releasing and adrenocorticotropic hormone (ACTH)-releasing adenomas. Functional adenoma was significantly more common in women; however, the incidence of non-functional adenoma was more in men (61%), indicating the correlation between gender and subtype of adenoma (P = 0.008). Most tumors were functional microadenomas (69%), while macroadenomas were primarily non-functional (50%). The HIT-6 scores demonstrated that functional microadenomas had higher HIT-6 scores and patients with prolactinoma experienced more severe headaches than other subtypes (P = 0.003). Conclusion: Our study revealed significant effects of the type of adenoma on the severity of headaches, as patients with functional microadenomas had more muscular headaches. Additionally, the hormonereleasing function of tumors plays a vital part in the advent and severity of adenoma-related headaches. [ABSTRACT FROM AUTHOR]

Background: Prolactinomas are common tumours that significantly reduce quality-of-life (QOL) due to sellar mass effect, secondary hypogonadism, and the peripheral effects of prolactin. Understanding the factors that influence QOL would provide insights into therapeutic targets to optimise patient outcomes and improve wellbeing in prolactinoma. Methods: A systematic review was performed in accordance with the PRISMA statement. Studies that reported patient QoL using validated metrics were included. Bias and methodological rigour were assessed using the MINORS criteria. Results: A total of 18 studies were identified studies were available for review, comprising 877 patients. Most were small cross-sectional studies at high risk of bias. Prolactinoma exhibit worse QOL than healthy controls, particularly mental and psychosocial wellbeing. QOL is also worse than patients with non-functional adenomas, but better than those with Cushing's disease and acromegaly. QOL correlates with prolactin levels, and approaches population baseline with prolonged biochemical control. Dopamine agonists and surgery both improve overall QOL, however improvements are more rapid with surgery. Conclusion: Poor quality of life in prolactinoma is multifactorial, related to biochemical control, side effects of therapy, and sellar mass effect. Targeting persistent symptoms, reducing healthcare costs, and reducing side-effects of therapy are avenues to improving QOL in patients with prolactinoma. [ABSTRACT FROM AUTHOR]

Purpose: Prolactin (PRL)-secreting tumours are associated with infertility and can be reverted by dopamine agonist (DA) therapy. The suspension of DA is recommended once pregnancy is established, as all DAs cross the placenta. The aim of the study was to evaluate the rate of maternal-foetal complications in women treated with cabergoline (CAB) or bromocriptine (BRM) for prolactinoma during gestation and the effect of pregnancy on prolactinoma progression. Methods: This was a retrospective observational study involving 43 women affected by prolactinoma who became pregnant during therapy with CAB or BRM for a total of 58 pregnancies. For each patient, medical records were analysed by integrating the data with outpatient or telephone interview. Results: At the time of conception, 18 women were in the BRM group, while 40 were in CAB group. No differences were found in obstetric or neonatal outcomes between the two groups. There was a significant difference (p = 0.046) in child complications reported in maternal interview found exclusively in the CAB group. No further confounding factors were detected. Disease remission rate after the first pregnancy was 42.9% and the main predictor was a lower PRL nadir before pregnancy (p = 0.023). No difference was detected between the two groups in terms of tumor remission. Breastfeeding did not modify the outcome. Conclusion: Foetal exposure to DAs during the first weeks of embryogenesis is not associated with a greater risk of complications. The transient and mild developmental disorders recorded resolved spontaneously and the prevalence was substantially overlapping with that observed in the general population. [ABSTRACT FROM AUTHOR]

Objective 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. Methods A single-center series of 290 cases was analyzed retrospectively and clinical data were collected. Intratumoral collagen content was assessed by Masson trichrome staining. Results 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). Conclusion 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. [ABSTRACT FROM AUTHOR]

Context The Roche prolactin immunoassay is used throughout the world. It reports higher values than the Siemens immunoassay but the manufacturer-defined reference intervals are similar. Patient results are often above the Roche upper limit but within the Siemens interval, causing diagnostic confusion. Objective Establish new reference intervals for the Roche and Siemens prolactin immunoassays. Methods We established new reference intervals for the Roche and Siemens immunoassays using 374 specimens from healthy outpatients. We performed chart review for unnecessary testing and treatment for 298 patients in a 6-month period with at least 1 Roche prolactin value above the manufacturer-defined upper limit and below our new upper limit. Results The new upper limit for the Roche assay was 37.8 ng/mL (females) and 22.8 ng/mL (males). The manufacturer-defined limits were 23.3 ng/mL and 15.2 ng/mL, respectively. New intervals for the Siemens assay matched the manufacturer. No cases of clinically significant pathophysiologic prolactin excess were identified in patients with values between the manufacturer-defined upper reference limit and our new Roche upper limit. Unnecessary further evaluation in these patients included 459 repeat prolactin measurements, 57 macroprolactin measurements, 39 magnetic resonance imaging studies, and 28 endocrine referrals. Eleven patients received dopamine agonists. The minimum cost of excess care using Medicare reimbursement rates was $34 134, with substantially higher amounts billed to patients and their insurance providers. Conclusion Adoption of new upper reference limits for the Roche prolactin assay of 37.8 ng/mL (females) and 22.8 ng/mL (males) would not delay diagnosis or necessary intervention in patients with clinically significant pituitary tumors but would reduce unnecessary evaluation in patients without pathophysiologic prolactin excess. [ABSTRACT FROM AUTHOR]

We explored the effects of curcumin on the aberrant biological behaviors of prolactinoma cells and the downstream pathways through which curcumin exerts its antitumor effects. We used quantitative reverse transcription‐polymerase chain reaction assays to measure miR‐206 expression levels in peripheral blood samples from patients with prolactinoma before and after curcumin treatment. We also investigated the proliferation level, viability, and invasion ability of groups of cells treated with different concentrations of curcumin using 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3‐di‐phenytetrazoliumromide (MTT) assays, cell cloning assays, and Transwell assays, respectively. Furthermore, we determined the levels of autophagy‐related proteins and protein kinase B/mammalian target of the rapamycin (Akt/mTOR) signaling pathway‐related proteins in each group of treated cells by western blot. Curcumin treatment upregulated miR‐206 expression levels in the peripheral blood of patients with prolactinoma and in GH3 cells. Knockdown of miR‐206 expression enhanced the proliferation and invasive ability of GH3 cells, while curcumin treatment effectively inhibited the aberrant biological behavior of GH3 cells enhanced by miR‐206 knockdown. miR‐206 knockdown also activated the Akt/mTOR signaling pathway and inhibited autophagy in GH3 cells, and these changes were effectively reversed by curcumin treatment. Thus, curcumin inhibited the Akt/mTOR signaling pathway and promoted cell autophagy by miR‐206 upregulation, resulting in antitumor effects that inhibited prolactinoma cell proliferation and invasion. [ABSTRACT FROM AUTHOR]

Purpose: 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). Methods: 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. Results: 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). Conclusions: 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. [ABSTRACT FROM AUTHOR]

Pituitary carcinomas are rare but associated with significant morbidity and mortality. They remain challenging to diagnose and manage. In this case, we describe a 56-year-old man who presented with erectile dysfunction and binocular vertical diplopia. He had central hypogonadism, secondary adrenal insufficiency, and central hypothyroidism on biochemical testing. His serum prolactin was 1517 mcg/L (1517 ng/mL; reference range 4-15 mcg/L), and his sellar magnetic resonance imaging showed a 2.0 × 2.2 × 3.1 cm pituitary tumor. Pathology revealed a prolactin-secreting carcinoma. Despite treatment with a high-dose dopaminergic, 2 transsphenoidal resections, and 1 course of radiation, prolactin levels continued to rise. He developed metastases to the epidural space and thecal sac from the thoracic to sacral spine, for which he received 12 cycles of temozolomide chemotherapy with initial clinical and biochemical response. This was followed by disease escape and progression. We discuss the clinical and imaging features that warrant a high index of suspicion for pituitary carcinoma and review contemporary treatment. [ABSTRACT FROM AUTHOR]

Diabetes Mellitus (DM) is a persistent metabolic disorder characterised by elevated glucose concentration in blood. Approximately, 422 million individuals globally suffer from diabetes, with the majority residing among middle-class and lower-class countries as per the reports of World Health Organisation (WHO) 2023. Strict blood sugar control in conjunction with high-dose insulin therapy might potentially prevent or delay the progression of microvascular issues, lower overall mortality, and lessen the chance of macrovascular problems. These conclusions were supported by the Diabetes Control and Complications Trial and the large longitudinal investigation known as the epidemiology of diabetes and its complications. Numerous drugs and receptors involved in glucose metabolism are currently being used to treat diabetes, including a-Glucosidase inhibitors, dopamine D-2 agonists, biguanides, glinides, amylin analogues, Peroxisome Proliferator-activated Receptors (PPARs), Glucagon-like Peptide-1 (GLP-1), and biguanides. Due to the associated side effects and the financial difficulties in obtaining traditional antidiabetic regimens, the current review has placed a higher priority on investigating novel molecular targets for the development of antidiabetic medications intended to manage the progression of the illness. This emphasises how important it is to find new molecular targets associated with the illness's onset instead of only treating its symptoms or outward signs. [ABSTRACT FROM AUTHOR]

Purpose: To describe a series of cases with pharmacological hyperprolactinemia in primary care setting and the prolactin levels, clinical implications of different causes of pharmacological hyperprolactinemia. Methods: A retrospective study of all patients with detected hyperprolactinemia in hormonal studies was performed between 2019 and 2020 in 20 Spanish primary care centers. Hyperprolactinemia is defined as a serum prolactin >19.4ng/ml in men and >26.5ng/ml in women. Four pharmacological causes of hyperprolactinemia were established: (i) oral contraceptives (OCPs) and other hormonal treatments; (ii) antipsychotics and antidepressants; (iii) other drugs (calcium antagonists, antiemetics, H2 antihistamines, opioids, and anabolic agents); and (iv) hyperprolactinemia due to several drugs. Results: From a sample of 501 patients with elevated serum prolactin, 39.4% (n=162) had pharmacological hyperprolactinemia. The most common cause of pharmacological hyperprolactinemia in women was OCPs (n=61) while in men antipsychotics/antidepressants (n=21). In the cases of hyperprolactinemia due to antipsychotics/antidepressants, the prolactin levels were significantly higher in patients taking classical antipsychotics than in those taking second-generation antipsychotics (80.0±43.17 vs. 50.7±28.66 ng/dL, P=0.035). The antidepressant/antipsychotic group showed hyperprolactinemia-related symptoms more frequently than the group of other treatments (58.9% vs. 32%, P=0.001). The concomitant use of several drugs caused hyperprolactinemia-related symptoms more frequently than one drug alone (73% vs. 44%, P=0.031). Conclusion: In this series of cases, drugs represented the 39.4% of the causes of hyperprolactinemia. The most common drugs were OCPs in women and antipsychotics/antidepressants in men. Antidepressants/antipsychotics were drugs that caused the greatest elevation of the prolactin levels and showed hyperprolactinemia-related symptoms more frequently. [ABSTRACT FROM AUTHOR]

Elevated serum prolactin concentrations occur in inherited disorders of biogenic amine metabolism because dopamine deficiency leads to insufficient inhibition of prolactin secretion. This work from the International Working Group on Neurotransmitter Related Disorders (iNTD) presents the results of the first standardized study on levodopa‐refractory hyperprolactinemia (LRHP; >1000 mU/L) and pituitary magnetic resonance imaging (MRI) abnormalities in patients with inherited disorders of biogenic amine metabolism. Twenty‐six individuals had LRHP or abnormal pituitary findings on MRI. Tetrahydrobiopterin deficiencies were the most common diagnoses (n = 22). The median age at diagnosis of LRHP was 16 years (range: 2.5–30, 1st–3rd quartiles: 12.25–17 years). Twelve individuals (nine females) had symptoms attributed to hyperprolactinemia: menstruation‐related abnormalities (n = 7), pubertal delay or arrest (n = 5), galactorrhea (n = 3), and decreased sexual functions (n = 2). MRI of the pituitary gland was obtained in 21 individuals; six had heterogeneity/hyperplasia of the gland, five had adenoma, and 10 had normal findings. Eleven individuals were treated with the dopamine agonist cabergoline, ameliorating the hyperprolactinemia‐related symptoms in all those assessed. Routine monitoring of these symptoms together with prolactin concentrations, especially after the first decade of life, should be taken into consideration during follow‐up evaluations. The potential of slow‐release levodopa formulations and low‐dose dopamine agonists as part of first‐line therapy in the prevention and treatment of hyperprolactinemia should be investigated further in animal studies and human trials. This work adds hyperprolactinemia‐related findings to the current knowledge of the phenotypic spectrum of inherited disorders of biogenic amine metabolism. [ABSTRACT FROM AUTHOR]

(1) Background: There is a lack of direct evidence on whether SARS-CoV-2 affects women's sexual function through a biological-organic mechanism. Existing studies on the topic are few and have produced contradictory results. This study aims to explore the possible relationship between sex hormones and sexual function in patients who have been infected with SARS-CoV-2. Moreover, we aimed to determine whether these changes are related to the clinical course of COVID-19 and whether they are temporary or long-lasting. (2) Methods: A study was conducted on 104 women, including 64 women infected with COVID-19 and a control group of 40 healthy women, between January 2021 and August 2022. Blood samples were collected to measure prolactin and oxytocin levels, and a clinical assessment was performed 3 and 6 months later. Sexual function self-assessment was captured based on the FSFI scale. (3) Results: Our study found that patients with severe COVID-19 had better sexual satisfaction scores one month after recovery but no discernible difference after six months. High levels of serum prolactin were observed in patients with active COVID-19 but became similar to a control group after one month and remained stable over time. Higher prolactin levels were significantly associated with increased arousal and hydration. Individuals with severe COVID-19 had notably low levels of plasma oxytocin, but there was no correlation between oxytocin levels and sexual satisfaction. (4) Conclusions: The gynecologic symptoms, as well as disturbances in oxytocin and prolactin levels, might be observed in a short time after infection. However, SARS-CoV-2 infection has no lasting effect on sexual function, oxytocin, and prolactin levels among women. [ABSTRACT FROM AUTHOR]

Background: Prolactinomas (PRLs) are prevalent pituitary adenomas associated with metabolic changes and increased cardiovascular morbidity. This study examined clinical, endocrine, metabolic, and inflammatory profiles in PRL patients, aiming to identify potential prognostic markers. Methods: The study comprised data from 59 PRL patients gathered in a registry at the University Hospital of Zurich. Diagnostic criteria included MRI findings and elevated serum prolactin levels. We assessed baseline and follow-up clinical demographics, metabolic markers, serum inflammation-based scores, and endocrine parameters. Treatment outcomes were evaluated based on prolactin normalization, tumor shrinkage, and cabergoline dosage. Results: The PRL cohort exhibited a higher prevalence of overweight/obesity, prediabetes/diabetes mellitus, and dyslipidemia compared to the general population. Significant correlations were found between PRL characteristics and BMI, HbA1c, and fT4 levels. Follow-up data indicated decreases in tumor size, tumor volume, prolactin levels, and LDL-cholesterol, alongside increases in fT4 and sex hormones levels. No significant associations were observed between baseline parameters and tumor shrinkage at follow-up. A positive association was noted between PRL size/volume and the time to achieve prolactin normalization, and a negative association with baseline fT4 levels. Conclusion: This study underscores the metabolic significance of PRL, with notable correlations between PRL parameters and metabolic indices.However, inflammatory markers were not significantly correlated with patient stratification or outcome prediction. These findings highlight the necessity for standardized follow-up protocols and further research into the metabolic pathogenesis in PRL patients. [ABSTRACT FROM AUTHOR]

A 10-yr-old female was referred due to prolonged bleeding lasting for a week following tooth extraction. She had heavy periods since she was 9. Her height was < 0.4th centile. Tanner staging was breast stage B3-4, axillary hair A1, and pubic hair P1. Thyroid function tests showed elevated TSH, low free T4, and negative anti-TPO antibodies. Gonadotrophins showed high FSH and a prepubertal LH. Prolactin was high and ovarian cysts were found on ultrasound. Further investigations revealed low von Willebrand factor (vWF) antigen levels, leading to a diagnosis of acquired von Willebrand disease. She was started on levothyroxine therapy, with normalization of vWF antigen levels, prolactin levels, cessation of her menstrual periods and resolution of ovarian cysts. [ABSTRACT FROM AUTHOR]

Pregnancy is a period in which the anatomy and physiology of the pituitary gland change significantly. Normal pituitary gland functions are necessary for fertility and the continuation of pregnancy. The presence of a pituitary disease requires management with a multidisciplinary approach to protect the health of the mother and fetus, and it is recommended that these patients become pregnant in a planned manner. Treatment should be considered before pregnancy for pituitary adenomas with a risk of growth. Non-contrast magnetic resonance imaging (MRI) may be performed safely during pregnancy, but the ideal approach is to postpone the MRI until after the birth if possible, and if it is not possible, to take it without contrast. If there are no signs of compression in pituitary adenomas, no treatment is necessary during pregnancy. However, due to increased fetal and maternal morbidity and mortality in Cushing’s disease, treatment is necessary even if there is no compression. In the presence of compression findings, dopamine agonists can be used in all types of pituitary adenomas. Surgery may be performed in the second trimester for pituitary adenomas that cause compression unresponsive to medical treatment and for Cushing’s disease. In pregnant women with pituitary insufficiency, replacement doses should be adjusted according to the gestational week. The diagnosis and treatment of pituitary diseases in this period is more complex and specific than in the nonpregnant period and require a multidisciplinary approach. [ABSTRACT FROM AUTHOR]