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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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The widespread use of diagnostic imaging has led to an increase in the incidence of pituitary tumors. The majority of incidentalomas are hormone-inactive (HI) pituitary microadenomas. The most common clinically relevant pituitary adenomas are prolactin-secreting, followed by HI, and far less common are growth hormone (GH)-, adrenocorticotropic hormone (ACTH)- and thyroid-stimulating hormone (TSH)-secreting adenomas. Pituitary adenomas are usually benign, although aggressive growth and invasion occurs in individual cases. Very rarely, they give rise to metastases and are then termed pituitary carcinomas. All pituitary tumors require endocrine testing for pituitary hormone excess. In addition to the medical history and clinical examination, laboratory diagnostics are very important. Symptoms such as irregular menstruation, loss of libido or galactorrhea often lead to the timely diagnosis of prolactinomas, and hyperprolactinemia can easily confirm the diagnosis (considering the differential diagnoses). Diagnosis is more difficult for all other hormone-secreting pituitary adenomas (acromegaly, Cushing's disease, TSHoma), as the symptoms are often non-specific (i.e., headaches, weight gain, fatigue, joint pain). Furthermore, comorbidities such as hypertension, diabetes, and depression are such widespread diseases that pituitary adenomas are rarely considered as the underlying cause. Timely diagnosis and appropriate treatment have a significant impact on morbidity, mortality, and quality of life. Therefore, the role of primary care physicians is very important for achieving an early diagnosis. In addition, patients with pituitary adenomas should always be referred to endocrinologists to ensure optimal diagnosis as well as treatment., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Pituitary adenomas are rare in children and young people under the age of 19 (hereafter referred to as CYP) but they pose some different diagnostic and management challenges in this age group than in adults. These rare neoplasms can disrupt maturational, visual, intellectual and developmental processes and, in CYP, they tend to have more occult presentation, aggressive behaviour and are more likely to have a genetic basis than in adults. Through standardized AGREE II methodology, literature review and Delphi consensus, a multidisciplinary expert group developed 74 pragmatic management recommendations aimed at optimizing care for CYP in the first-ever comprehensive consensus guideline to cover the care of CYP with pituitary adenoma. Part 2 of this consensus guideline details 57 recommendations for paediatric patients with prolactinomas, Cushing disease, growth hormone excess causing gigantism and acromegaly, clinically non-functioning adenomas, and the rare TSHomas. Compared with adult patients with pituitary adenomas, we highlight that, in the CYP group, there is a greater proportion of functioning tumours, including macroprolactinomas, greater likelihood of underlying genetic disease, more corticotrophinomas in boys aged under 10 years than in girls and difficulty of peri-pubertal diagnosis of growth hormone excess. Collaboration with pituitary specialists caring for adult patients, as part of commissioned and centralized multidisciplinary teams, is key for optimizing management, transition and lifelong care and facilitates the collection of health-related quality of survival outcomes of novel medical, surgical and radiotherapeutic treatments, which are currently largely missing., (© 2024. Springer Nature Limited.)

Objective and Design: Macroprolactinemia may influence the interpretation of serum prolactin levels-a recognised phenomenon since 1981. The degree of macroprolactinaemia over time is less well described. We determined how macroprolactin status (based on polyethylene glycol (PEG) precipitation) varied by analysing serial measurements in hyperprolactinaemic individuals over a period of 9 years., Patients and Measurements: Results from 1810 individuals were included. All serum total prolactin results (measured using Roche Cobas 8000 analyser) were extracted from the laboratory information system for the period 1 January 2012 to 1 April 2021, along with relevant patient demographic/test data. Samples with a macroprolactin screening test performed (on samples with prolactin > 700 miu/L) were included in the main analysis., Results: During the study period, 2782 macroprolactin checks were performed (12.5% of all prolactin tests) in 1810 individuals (599 males/2183 females, median-age: 35, interquartile range: 25-47, range: 16-93 years). Multiple macroprolactin checks were carried out on 465 patients (1437 measurements) with 94 patients (141 measurements) screening positive (<60% recovery). Only 19 patients (18 female) had at least one result above and one below the 60% screening cut-off, with 10 of these patients having results close to the 60% cut-off; in 9 patients, results were clearly different between repeat samples. In seven cases, the adjusted monomeric prolactin showed a potentially clinically significant difference., Conclusions: In this study, only 19/465 patients appeared to change macroprolactin status based on a 60% PEG recovery cut-off. The majority of these 19 patients were on antipsychotic/antidepressant medication(s) or had a prolactinoma; in only 7 did monomeric prolactin change significantly. This suggests that once macroprolactin status has been determined, clinical decision making is rarely affected by repeating it., (© 2024 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correctcause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Societyof Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.

The main treatment option of prolactin-secreting pituitary adenomas is dopamine agonist therapy, which demonstrates prolactin level normalizing and reducing the size of an adenoma in the majority of cases. However, significant amount of patients - about 20% - poorly responds even to high doses of dopamine agonists that is explained by the resistance to therapy. The occurrence of pharmacodynamic characteristics is one of the causes responsible for the development of resistance to typical therapy. Clinical manifestations of persistent hyperprolactinemia are due to following pathological factors: hormonal hypersecretion and the mass-effect of pituitary adenoma. Prevention of irreversible changes is possible only with timely detection of resistance and determination of the optimal personalized treatment algorithm.We report a clinical case of dopamine-agonist resistant microprolactinoma. Patient's health stabilisation, normal level of prolactin and reduction in size of adenoma were achieved due to administration of combined treatment with tamoxifen and dopamine agonists. Hyperprolactinaemia occurring because of prolactin-secreting pituitary adenoma and associated adverse effects are significant problem, decreasing quality of life and demographics in general. This underlines the importance of figuring out causes and identifying predictors of the therapy resistance.The results of the study, illustrated by a clinical example, are presented in the present paper.

Introduction: Prolactinomas are the most common type of pituitary gland tumors that secrete overly prolactin. They account for approximately 60% of all hormone-secreting hypophysis tumors., Aim: This study aims to analyze gender differences in patients with prolactinomas who were operated on transsphenoidal surgery and conduct a single-center retrospective analysis of patient data., Material and Methods: This study evaluated the medical records of 109 patients (61 females and 48 males) from 2009 to 2019 at Feofaniya Clinical Hospital of the State Administration of Affairs in Kyiv, Ukraine. The primary criterion for including patients was a Serum Prolactin (PRL) level of over 100 ng/ml and the presence of a pituitary adenoma (PA) as observed on MRI. Additionally, the histological examination needed to confirm the presence of Prolactin-Secreting Pituitary Adenomas (PSPAs) without plurihormonal activity through both microscopy and immunohistochemical (IHC) staining., Results: Significant differences in preoperative PRL levels were not observed. However, males had significantly larger tumor sizes and prevalence of macroadenomas. In male patients, the preoperative PLR levels showed a weak negative correlation with age (r=-0.304, p < 0.036) and a positive correlation with tumor size (r=0.555, p < 0.001) and cavernous sinus invasion (r=0.339, p < 0.018). In females, preoperative PRL was significantly associated only with tumor size and Knosp grade., Conclusion: Prolactin-Secreting Pituitary Adenomas (PSPAs) are more common in women than men and are characterized by larger and more invasive tumors with high PRL levels at diagnosis. The PRL level and tumor size before surgery can predict early biochemical remission in both males and females with an accuracy of 58.3% and 68.8%, respectively., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The occurrence of prolactinomas in sex hormone treated patients with central hypogonadism is extremely rare., Case Presentation: We present a Caucasian male patient who was diagnosed with Kallmann syndrome (KS) at age 15 years. Testosterone treatment was started. At age 26 the patient presented with mild headache. MRI revealed two separate pituitary adenomas along with the absence of the olfactory bulbs. Given the presence of marked hyperprolactinemia (17x upper limit of the reference range) the diagnosis prolactinoma was made and treatment with cabergoline was started which resulted in a complete biochemical response and in marked reduction of both adenomas in size. Hypogonadism persisted and testosterone replacement therapy was continued. Genetic testing of genes associated with pituitary tumors, Kallmann syndrome and idiopathic hypogonadotropic hypogonadism was negative. Mild concomitant hypercalcemia in accordance with familial hypocalciuric hypercalcemia (FHH) prompted mutation analysis of the calcium receptor ( CASR) gene which yielded a pathogenic inactivating variant., Discussion/conclusion: The presence of two separate prolactinomas in a patient with KS has not yet been reported in the literature. The effect of sex hormone treatment of KS patients on the possible development of prolactinoma is unknown at present. The occurance of multiple prolactinomas in our patient suggests increased susceptibility. Although CaSR is expressed in GnRH neurons in mouse brain and CaSR deficient mice have a reduced hypothalamic GnRH neuronal population, the relevance of the CASR gene variant in our patient for the KS phenotype is unclear at present., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jensterle, Janež, Vipotnik Vesnaver, Debeljak, Breznik, Trebušak Podkrajšek, Herman, Fliers, Battelino and Avbelj Stefanija.)

Background: Men harboring prolactinomas frequently suffer from central hypogonadism with secondary anemia. They present insidious and nonspecific symptoms of hypogonadism, making it difficult to diagnose the disease and determine its duration. The result is a delay in diagnosis, which may have harmful hormonal and metabolic consequences. We hypothesized that a decrease in hemoglobin (HB) levels prior to prolactinoma diagnosis, may signal hyperprolactinemia onset and estimate disease duration., Methods: We retrospectively evaluated the prediagnosis temporal trends in HB levels of 70 males with prolactinoma, diagnosed from January 2010 to July 2022. Men without hypogonadism, patients that received testosterone, and those with unrelated anemia were excluded., Results: Sixty-one of seventy men (87%) with prolactinoma presented with hypogonadism, and forty men (57%) had HB levels ≤13.5 g/dL at diagnosis. We identified 25 patients with "informative" HB curves (mean age, 46.1±14.9 years; median prolactin, 952 ng/mL; median follow-up, 14.0 years), demonstrating an obvious prediagnosis HB decrease (greater than 1.0 g/dL), from a prediagnosis baseline HB of 14.4 ± 0.3 to 12.9 ± 0.5 g/dL at diagnosis. The median "low-HB duration" (from the first low HB measurement to hyperprolactinemia diagnosis) was 6.1 years (IQR, 3.3-8.8 years). In symptomatic patients, we identified a correlation between "low-HB duration" and patient-reported sexual dysfunction duration (n = 17, R = 0.502, p = 0.04). The "low-HB duration" was significantly longer than the reported sexual dysfunction duration (7.0 ± 4.5 vs. 2.9 ± 2.5 years, p = 0.01)., Conclusions: In our cohort of men with prolactinomas and hypogonadism, we found a marked decrease in HB levels that preceded prolactinoma diagnosis by a median of 6.1 years, with a mean delay of 4.1 years between HB decrease and hypogonadal symptoms appearance. These results suggest that HB decline prior to prolactinoma diagnosis may serve as a marker for hyperprolactinemia onset in a subset of hypogonadal men and allow a more accurate assessment of disease duration., (© 2023 American Society of Andrology and European Academy of Andrology.)

Prolactinomas are the most common pituitary tumor histotype, with microprolactinomas being prevalent in women and macroprolactinomas in men. Hyperprolactinemia is among the most common causes of hypogonadotropic hypogonadism in both sexes, prompting medical advice for hypogonadism (infertility, oligo-amenorrhea, impotence, osteoporosis/osteopenia) in both sexes, and for signs and symptoms of mass effects (hypopituitarism, visual loss, optic chiasm compression, cranial nerve deficits, headaches) predominantly in men. Diagnostic workup involves a single prolactin measurement and pituitary imaging, but some laboratory artifacts (ie, the "hook effect" and macroprolactin) can complicate or delay the diagnosis. The treatment of choice for prolactinomas is represented by dopamine agonists, mainly cabergoline, which are able to induce disease control, restore fertility in both sexes, and definitively cure one-third of patients, thus permitting treatment discontinuation. Pregnancy and menopause may promote spontaneous prolactin decline and anticipate cabergoline discontinuation in women. Surgery and/or radiotherapy are indicated in case of resistance to cabergoline not overcome by the increase in drug dose up to the maximally tolerated or the patient's personal choice of surgery. The evidence of resistance to cabergoline in invasive and proliferative tumors may indicate biological aggressiveness, thus requiring alternative therapeutic approaches mainly based on temozolomide use as monotherapy or combined with radiotherapy. In uncontrolled patients, new medical approaches (alternative hormonal treatments, cytotoxic drugs, peptide receptor radionuclide therapy, mTOR/Akt inhibitors, tyrosine kinase inhibitors, or immunotherapy) may be offered but the experience collected to date is still very scant. This article reviews different facets of prolactinomas and discusses approaches to the condition in more common clinical situations., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Prolactinomas are the most common secreting adenomas of the pituitary. In 20% of cases resistance to dopamine-agonists treatment is observed. Medical therapy resistance causes progression of pathological symptoms of hyperprolactinemia and negative topographic and anatomical changes of prolactinoma. The causes of ineffectiveness of dopamine agonists therapy are not fully understood as well as approaches to managing patients require clarification. Current concepts of resistance are based on the data obtained as a result of surgery or after a period of long-term ineffective therapy. Thus, it is very important to find methods of assessing the sensitivity of prolactin-secreting adenomas to drug therapy before surgical treatment. Genetic and immunohistochemical studies find special place among these methods, making it possible to predict adenoma's response to drug therapy at early diagnostic stage. Obtained results will allow us to form personalized algorithm for managing patients.

Ectopic prolactin-secreting microadenomas are rare and management is often surgical in contrast to intrasellar pituitary prolactin-secreting microadenomas. We present a case of ectopic dopamine-resistant microprolactinoma treated with cabergoline which led to symptom resolution, hormonal remission, and cystic degeneration of the tumor. A 30-year-old active duty male presented with a chief complaint of inability to maintain an erection for 6 months. Initial workup revealed suppressed serum testosterone of 128.60 ng/ml with an elevated prolactin level at 275.10 ng/ml. Pituitary magnetic resonance imaging showed a small mass measuring 9 mm in the left cavernous sinus. Medical management was initiated with cabergoline, which was titrated over the course of a year from 0.5 mg a week to 3.5 mg a week at its peak before being weaned off completely at 54 months. After treatment, the patient's symptoms resolved, his prolactin decreased to 29.5 ng/ml, near-normal, and his tumor had decreased size with cystic degeneration. Management for any prolactinoma has three primary goals: remittance of symptoms, decrease in prolactin levels, and decrease in tumor size. These are achieved through primarily medical management or surgery. Even though ectopic microprolactinomas are still frequently addressed surgically, this case shows that medical therapy can successfully treat ectopic prolactin-secreting pituitary microadenomas even in cases of dopamine resistance., (© The Association of Military Surgeons of the United States 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Giant prolactinoma (> 4 cm in dimension) is a rare disorder. Invasive macroprolactinoma has the potential to cause base of skull erosion and extend into the nasal cavity or even the sphenoid sinus. Nasal bleeding caused by intranasal tumor extension is a rare complication associated with invasive giant prolactinoma. We report a case of giant invasive macroprolactinoma with repeated nasal bleeding as the initial symptom., Case Presentation: A 24-year-old man with an invasive giant prolactinoma in the nasal cavity and sellar region who presented with nasal bleeding as the initial symptom, misdiagnosed as olfactory neuroblastoma. However, markedly elevated serum prolactin levels (4700 ng/mL), and a 7.8-cm invasive sellar mass confirmed the diagnosis of invasive giant prolactinoma. He was treated with oral bromocriptine. Serum prolactin was reduced to near normal after 6 months of treatment. Follow-up magnetic resonance imaging showed that the sellar lesion had disappeared completely and the skull base lesions were reduced., Conclusion: This case is notable in demonstrating the aggressive nature of untreated invasive giant prolactinomas which can cause a diagnostic difficulty with potential serious consequences. Early detection of hormonal levels can avoid unnecessary nasal biopsy. Early identification of pituitary adenoma with nasal bleeding as the first symptom is particularly important., (© 2023. The Author(s).)

Importance: Pituitary adenomas are neoplasms of the pituitary adenohypophyseal cell lineage and include functioning tumors, characterized by the secretion of pituitary hormones, and nonfunctioning tumors. Clinically evident pituitary adenomas occur in approximately 1 in 1100 persons., Observations: Pituitary adenomas are classified as either macroadenomas (≥10 mm) (48% of tumors) or microadenomas (<10 mm). Macroadenomas may cause mass effect, such as visual field defects, headache, and/or hypopituitarism, which occur in about 18% to 78%, 17% to 75%, and 34% to 89% of patients, respectively. Thirty percent of pituitary adenomas are nonfunctioning adenomas, which do not produce hormones. Functioning tumors are those that produce an excess of normally produced hormones and include prolactinomas, somatotropinomas, corticotropinomas, and thyrotropinomas, which produce prolactin, growth hormone, corticotropin, and thyrotropin, respectively. Approximately 53% of pituitary adenomas are prolactinomas, which can cause hypogonadism, infertility, and/or galactorrhea. Twelve percent are somatotropinomas, which cause acromegaly in adults and gigantism in children, and 4% are corticotropinomas, which secrete corticotropin autonomously, resulting in hypercortisolemia and Cushing disease. All patients with pituitary tumors require endocrine evaluation for hormone hypersecretion. Patients with macroadenomas additionally require evaluation for hypopituitarism, and patients with tumors compressing the optic chiasm should be referred to an ophthalmologist for formal visual field testing. For those requiring treatment, first-line therapy is usually transsphenoidal pituitary surgery, except for prolactinomas, for which medical therapy, either bromocriptine or cabergoline, is usually first line., Conclusions and Relevance: Clinically manifest pituitary adenomas affect approximately 1 in 1100 people and can be complicated by syndromes of hormone excess as well as visual field defects and hypopituitarism from mass effect in larger tumors. First-line therapy for prolactinomas consists of bromocriptine or cabergoline, and transsphenoidal pituitary surgery is first-line therapy for other pituitary adenomas requiring treatment.

Aim: Prolactinoma is a pituitary adenoma that secretes prolactin. Approximately 40% of all pituitary adenomas are prolactinomas. According to size, they are divided into micro, macro and giant prolactinomas. In women, prolactinomas cause irregularities of the menstrual cycle such as amenorrhea, galactorrhea, weight gain, in both sexes they cause sterility, hypogonadism, decreased libido and depression. In macroadenomas, symptoms due to the compression of the surrounding structures are also manifested, such as headache, vomiting, lower chiasmatic syndrome and ophthalmoplegia. Loss of the visual field due to compression of the optic chiasm is caused by a tumor larger than 10-15 mm with suprasellar spreading, which breaks through the diaphragma sellae. Giant prolactinomas are larger than 40 mm and make up 1-5% of all prolactinomas., Case Report: In this article I present the case of a 38-year-old woman from Ukraine with advanced chiasmatic syndrome caused by a giant prolactinoma. The tumor is infiltrating the left cavernous sinus, causing left-sided amaurosis and right-sided temporal hemianopsia., Conclusion: Inferior chiasmatic syndrome is characterized by bitemporal hemianopsia, a deterioration of visual acuity, bilateral bow-tie descendent atrophy of the optic nerve disc, and hemianopic rigidity of the pupils. Macroprolactinomas occur more frequently in men than in women. The diagnosis is often delayed, probably because the symptoms of hyperprolactinemia are less obvious in men, while women tend to present earlier due to menstrual cycle irregularities. Prolactinomas usually have a good prognosis. Effective medical treatment with dopamine agonists is available. Knowledge of the prolactinoma symptoms could help the diagnosis of compressive lesions of the optic chiasm.

Objectives: To compare dry eye parameters in prolactinoma patients and healthy controls and evaluate their correlation with prolactin (PRL) levels and the duration of hyperprolactinemia., Materials and Methods: Consecutive patients with prolactinoma and healthy controls were included in the study. Schirmer, tear break-up time (TBUT), tear osmolarity values, and ocular surface disease index (OSDI) scores were evaluated for each patient. Follow-up time and total duration of hyperprolactinemia were recorded for prolactinoma patients., Results: The study included 39 eyes of 39 patients with prolactinoma and 39 eyes of 39 age- and gender-matched healthy controls. Prolactinoma patients showed lower Schirmer (14.1±8.4 vs. 24.8±8.9 mm; p<0.001) and TBUT values (7.0±3.2 vs. 11.6±2.6 s; p<0.001) and higher OSDI scores (20.6±16.6 vs. 5.8±2.4; p<0.001) compared to the healthy controls. While the mean osmolarity of the prolactinoma patients was 301.6±8.3 mOsm/L, it was 297.7±12.5 mOsm/L for the healthy controls (p=0.07). The duration of hyperprolactinemia in prolactinoma patients showed a negative correlation with Schirmer (r=-0.395; p=0.013) and TBUT values (r=-0.377; p=0.018) and a positive correlation with OSDI scores (r=0.337; p=0.036)., Conclusion: Prolactinoma patients had significantly lower Schirmer and TBUT levels and higher OSDI scores compared to the healthy controls, but no significant difference in tear osmolarity. The effect of high PRL levels on tear film function was duration-dependent., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2022 by Turkish Ophthalmological Association | Turkish Journal of Ophthalmology, published by Galenos Publishing House.)

Purpose: Giant prolactinoma (GP) in childhood and adolescence is a rare entity with scarce literature. We aimed to describe clinical features, biochemistry, radiology, genetics, management, and outcome in pediatric (≤ 20 years) GP., Methods: Retrospective record review of 18 pediatric GP patients from our center and systematic review including these and 77 from the literature (total cohort: 95)., Results: GP constituted 20% of our pediatric prolactinoma cohort. In the total cohort (age: 15.4 ± 3.5 years), the majority (77, 82.8%) were males. Mass effect symptoms (88.6%), and pubertal delay/arrest in males (82.1%) were frequent. Median basal prolactin was 8649 (3246-17,532) ng/ml and the maximum tumor dimension was 5.5 ± 1.5 cm. MEN1 and AIP mutations were noted in 7 (21.9%) and 6 (18.8%) patients, respectively. Males with central hypogonadism had baseline bi-testicular volume of 20.2 ± 8.4 cc, lower LH than FSH (-2.04 ± 0.9 vs. -0.7 ± 1.6 SDS, p = 0.0075), and mostly, normal inhibin B. Majority (49/76, 64.5%) received dopamine agonist (DA) as first-line treatment with additional therapy in 35% (17/49). DA monotherapy arm had less frequent central hypothyroidism (42.9% vs 87.1%, p = 0.002) and central adrenal insufficiency (7.1% vs 66.7%, p = 0.0003) than multimodal therapy. A smaller tumor dimension (4.7 vs. 5.7 cm, p = 0.04) was associated with normoprolactinemia on DA monotherapy and AIP mutations (33.3% vs. nil, p = 0.02) with multimodal therapy., Conclusion: GP is characterized by male predominance with frequent delay/arrest of puberty (82%), but relative sparing of the FSH-inhibin B axis in boys. DA monotherapy may be preferred as the first-line therapy in pediatric GP., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: It was aimed to compare the testosterone level during the treatment and the factors associated with the persistence of hypogonadism in prolactinoma., Material and Methods: Thirty-five patients with hypogonadism who were diagnosed with prolactinoma were recruited to this retrospective study. Age, hemoglobin, hematocrit, glucose, lipid parameters, prolactin, follicle-stimulating hormone, luteinizing hormone, total testosterone, and the adenoma size were compared at the baseline and 6th month of the treatment. The parameters were also compared between the patients with hypogonadism (n=8) and the patients without hypogonadism at the 6th month of the treatment (n=27). Correlation analysis was also performed in terms of parameters that may be associated with the testosterone levels at the 6th month of the treatment., Results: The mean current age of the whole study group was 45.6±13.0 years, and the mean adenoma size was 23.9±11.4 mm. Thirty patients had macroadenoma, and five patients had microadenoma. Eight patients (23%) had low testosterone levels and hypogonadism symptoms at the 6th month of the prolactinoma treatment. The adenoma size was larger in patients with persistent hypogonadism than the patients without hypogonadism at the 6th month of the treatment, while the prolactin levels were similar between the groups, and macroadenoma was detected in all patients with persistent hypogonadism. A negative correlation was found between the testosterone levels at the 6th month of the prolactinoma treatment with the adenoma size., Conclusion: Adenoma size is the prominent factor than prolactin levels for predicting persistent hypogonadism in patients with male prolactinoma.

Objective: To evaluate the combined predictive value of MRI criteria with the prolactin-volume-ratio (PVR) to differentiate prolactinoma from non-prolactinoma, in small sellar lesions with hyperprolactinemia., Methods: Retrospective analysis of 55 patients with sellar lesions of ≤15 mm diameter on MRI and hyperprolactinemia of ≤150 ng/mL, surgically treated between 2003 and 2020 at the Medical University of Vienna, with a conclusive histopathological report. Serum prolactin levels, extent of pituitary stalk deviation, size and volume of the lesion were assessed. The PVR was calculated by dividing the preoperative prolactin level by tumor volume., Results: Our study population consisted of 39 patients (71%) with a prolactin-producing pituitary adenoma (group A), while 16 patients (29%) had another type of sellar lesion (group B). Patients in group A were significantly younger (p=0.012), had significantly higher prolactin levels at diagnosis (p<0.001) as well as smaller tumor volume (p=0.036) and lower degree of pituitary stalk deviation (p=0.009). The median PVR was significantly higher in group A (243 ng/mL per cm 3 ) than in group B (83 ng/mL per cm 3 ; p=0.002). Furthermore, the regression operating characteristics analysis revealed a PVR >100 ng/mL per cm 3 to be predictive for distinguishing prolactin-producing lesions from other small sellar lesions., Conclusion: In patients with small sellar lesions, Prolactin-Volume-Ratios >100 represents a possible predictive marker for the diagnosis of prolactin-producing pituitary adenomas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cho, Vila, Marik, Klotz, Wolfsberger and Micko.)

Hyponatremia is an uncommon manifestation of pituitary adenomas. Herein, I report a case of syndrome of inappropriate antidiuresis (SIAD) caused by a macroprolactinoma that rapidly resolved with dopamine agonist therapy. A 29-year-old White woman presented with euvolemic, hypotonic hyponatremia, normal thyroid and glucocorticoid axes, and inappropriately concentrated urine. She was found to have a 1.2-cm sellar mass. Investigation of additional pituitary axes revealed an elevated prolactin level of 193.7 ng/mL. The SIAD experienced by the patient corrected rapidly with initiation of cabergoline. The patient could not tolerate dopamine agonist therapy, and after 1 year, she underwent transsphenoidal resection of the mass after the prolactin began to increase. Pathological examination confirmed the diagnosis of macroprolactinoma. There was no recurrence of the tumor, and the patient continued to have normonatremia and normoprolactinemia 7 years after her operation. To my knowledge, this is the first report in the literature of pathology-confirmed macroprolactinoma marked by SIAD that showed rapid normalization of water metabolism with dopamine agonist therapy., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Prolactin (PRL)-secreting tumors are the most common functional pituitary adenomas. They usually respond to dopamine agonist (DA) treatment, with PRL normalization and adenoma shrinkage. Our aim was to characterize patients with prolactinoma resistant to DA treatment., Methods: This retrospective case series included patients diagnosed with DA-resistant prolactinomas between 1993-2017 in three medical centers. Resistance was defined as PRL levels above three times the upper limit of normal (ULN) despite a weekly dose of ≥2 mg cabergoline (CAB). Clinical and biochemical information, and response to treatment, were retrieved from medical records., Results: Twenty-six patients were identified; 20 males. Of 25 macroadenomas, three were giant tumors (>40 mm) and 15 (57.7%) were invasive. The mean age at diagnosis was 31.8 ± 14.9 years (range: 13-62). The median maximal CAB dose was 3.5 mg/week (IQR, 2.5-5). Half the patients received only CAB in escalating doses, nine received CAB and underwent transsphenoidal surgery, and four underwent surgery and radiotherapy in addition to CAB treatment. PRL levels at baseline between patients treated only with CAB and those operated were (91.6 [51.1-296.7] vs. 73.1 [22.6-170.9] XULN p = 0.355), and under maximal CAB dose PRL levels between patients treated only with CAB and those operated were similar (5.77 [1.27-11.27] vs 5.27 (2.9-26) XULN p = 0.317). At the last visit patients who received combined therapy achieved lower PRL levels than those treated with DA only (5.22 [1.7-21.6] vs 1.1 [0.44-3.99] XULN p = 0.017) PRL normalization was attained in seven patients and levels below 3 × ULN in fourteen patients; the overall response was 56%., Conclusions: Resistant prolactinomas usually require a multi-modal treatment strategy. We were able to control 14/25 (56%) of resistant tumors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Malignant prolactinomas are very rare and are diagnosed when a prolactin-producing pituitary adenoma has metastasized. We report on a 54-year-old man with a history of macroprolactinoma transforming into a pituitary carcinoma secreting both prolactin and growth hormone with metastases to the stomach, bone, lungs, retroperitoneum, and kidney. Reviewing the literature, this case is the first reporting of a pituitary carcinoma with biopsy-proven paraneoplastic cast nephropathy. Symptoms and renal function improved following a course of palliative chemotherapy and radiotherapy. After 2 years, his disease progressed requiring further palliative treatment that was complicated by severe chest sepsis. He was not fit for further chemotherapy, receiving symptomatic relief in a hospice, and died soon after. The case highlights the importance of considering a patient's past medical history in the context of persistent unexplained renal impairment and systemic metastases when unexplained systemic symptoms and multi-organ involvement is present. The importance of renal biopsy for definitive diagnosis and before using potentially nephrotoxic chemotherapy is also highlighted. Renal diagnosis helped inform the decision to give chemotherapy, with the importance of this evidenced by an improvement in renal function following chemotherapy.

Background: Giant prolactinomas are rare in childhood and adolescence and represent a challenge in diagnosis and management., Case Presentation: A 15.7-year-old male adolescent presented with short stature and delayed puberty. On clinical examination, mild right central VII paresis, gait instability, decreased visual acuity, and impaired visual fields were noted. Investigations showed hyperprolactinemia (2209 ng/mL), secondary hypothyroidism, hypogonadotropic hypogonadism, and growth hormone deficiency. Imaging studies showed an enormous invasive skull base mass. Craniotomy was undertaken to debulk the tumor and perform biopsies. Histology revealed a very large atypical, prolactin-secreting pituitary macroadenoma, i.e., a giant prolactinoma. After commencing cabergoline treatment, prolactin concentrations decreased in 5 months and normalized 18 months later, while significant shrinkage of the tumor was observed. The diagnostic work-up for genetic syndromes often associated with sporadic macroadenomas was negative., Conclusion: Giant prolactinomas presenting with multiple pituitary hormone deficiencies in childhood or adolescence are rare and require prompt diagnosis and multidisciplinary management., (© 2022. Hellenic Endocrine Society.)

Background: Managing treatment-resistant aggressive giant prolactinoma can be challenging, as the diagnosis is often complex, and treatment beyond dopamine agonists, surgery, and radiotherapy is limited., Case Presentation: A 21-year-old Malay woman first presented to our hospital at the age of 16 years with 1-year history of reduced vision and 2 years of amenorrhea. Her baseline prolactin level was 255,894 µIU/mL with secondary hypogonadism, and pituitary magnetic resonance imaging revealed a giant prolactinoma (2.8 × 3.2 × 4.2 cm 3 ) with suprasellar extension and optic chiasmal compression. She was initially treated with cabergoline, and reductions in the prolactin level and tumor mass were achieved, leading to vision improvement and resumption of normal menstruation. However, she developed recurrent tumor growth and hyperprolactinemia, causing relapse of symptoms, and she needed surgery. Eventually, despite three tumor debulking surgeries and escalation of cabergoline doses up to 1 mg/day, her tumor progressed with aggressive characteristics. Following a multidisciplinary meeting, the patient is initiated on temozolomide therapy after considering the long-term side effects of radiotherapy in her case., Conclusion: This case highlights the importance of early identification of treatment-resistant prolactinoma and the need for a multidisciplinary approach in managing aggressive prolactinoma in young patients, particularly regarding timely implementation of temozolomide therapy., (© 2022. The Author(s).)

Prolactinomas are the most common secretory tumor of the pituitary gland. Clinical symptoms may be due to prolactin oversecretion, localized mass effect, or a combination of both. Although the mainstay of prolactinoma management is medical therapy with dopamine agonists, endoscopic endonasal or transcranial surgery, radiation therapy, or a combination of these is an important treatment option in select cases. This article discusses prolactinoma phenotypes, clinical presentations, and clinically pertinent medical and surgical considerations when managing these tumors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Preoperative diagnosis of prolactinomas is critical because dopamine agonists have been regarded as a primary treatment. However, serum prolactin level alone is suboptimal for differentiating prolactinomas from hyperprolactinemia-causing non-functioning pituitary adenomas (NFPAs). By using the tumor size, the authors tried to investigate an effective parameter for the discrimination., Methods: We performed a retrospective review of patients who underwent trans-sphenoidal surgery for pituitary lesions in a single institute between January 2015 and May 2021. Using receiver operating curve (ROC) analyses, we compared performances of serum prolactin levels (PRL), a ratio of serum PRL levels to maximal tumor diameter (MD) (PRL/MD; PDR1), and MD squared (PRL/[MD] 2 ; PDR2) in preoperative diagnosis of prolactinomas., Results: A total of 223 patients with NFPAs (n = 175) and prolactinomas (n = 48) were included in the analysis. A moderate correlation was found between serum prolactin levels and MDs in prolactinomas (Pearson's r prl  = 0.43, P = 0.002), whereas a weak correlation was observed in NFPAs (Pearson's r nfpa  = 0.17, P = 0.028). Among diagnostic parameters, PDR2 exhibited the optimal diagnostic performance with the cutoff value of 0.83 [㎍/L]/mm 2 (area under the curve [AUC] = 0.945), compared with the PDR1 (8.93 [㎍/L]/mm with AUC 0.938) and PRL (99.4 ㎍/L with AUC 0.910). In the external validation study, PDR2 maintained superior performance over PDR1 and PRL (accuracy of 94.8%, 91.8%, and 75.8%, respectively)., Conclusions: PDR2 was a more effective indicator than prolactin alone in the preoperative differential diagnosis of prolactinomas and NFPAs, which may help select patients who need medical treatment first., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Prolactinomas are the most frequent pituitary adenomas. Prolactinoma may occur in different clinical settings and always require an individually tailored approach. This is the reason why a panel of Italian neuroendocrine experts was charged with the task to provide indications for the diagnostic and therapeutic approaches that can be easily applied in different contexts. The document provides 15 recommendations for diagnosis and 54 recommendations for treatment, issued according to the GRADE system. The level of agreement among panel members was formally evaluated by RAND-UCLA methodology. In the last century, prolactinomas represented the paradigm of pituitary tumors for which the development of highly effective drugs obtained the best results, allowing to avoid neurosurgery in most cases. The impressive improvement of neurosurgical endoscopic techniques allows a far better definition of the tumoral tissue during surgery and the remission of endocrine symptoms in many patients with pituitary tumors. Consequently, this refinement of neurosurgery is changing the therapeutic strategy in prolactinomas, allowing the definitive cure of some patients with permanent discontinuation of medical therapy.

Objective: To determine prevalence of hyperprolactinemia and prolactinoma among men presenting for initial fertility evaluation., Methods: We performed a retrospective review of men presenting for initial fertility evaluation at a tertiary care, academic health system between 1999 and 2018. Men with measured prolactin levels were analyzed to determine prevalence of hyperprolactinemia and prolactinoma. We compared clinical characteristics of men with and without hyperprolactinemia. Univariable and multivariable analysis were used to determine factors associated with hyperprolactinemia. We assessed effects of hyperprolactinemia and prolactinoma on testosterone levels, semen parameters and pregnancy outcomes after treatment., Results: A total of 3101 men had serum prolactin level measured. 65 (2.1%) had hyperprolactinemia. Patients with hyperprolactinemia had lower testosterone (median 280 ng/dL vs 313 ng/dL, P = 0.038) and lower total motile sperm count (median 7.0 million vs 34.7 million, P = 0.001) compared to men without hyperprolactinemia. 43.1% of men with hyperprolactinemia had oligospermia vs 21.5% of men without hyperprolactinemia (P<0.001). Univariable analysis demonstrated that men with elevated luteinizing hormone (LH) (OR 1.077, P = 0.001) and follicle-stimulating hormone (FSH) (OR 1.032, P = 0.002) were more likely to have hyperprolactinemia. Men with oligospermia were more likely to have hyperprolactinemia (OR 2.334, P = 0.004). On multivariable analysis, neither hormone parameters nor oligospermia were associated with elevated prolactin (P>0.05). Of the 65 men with hyperprolactinemia, 11 (17%) were diagnosed with a prolactinoma, resulting in an overall prevalence of 11 in 3101 (0.35%)., Conclusion: The overall prevalence of prolactinoma in our cohort of men undergoing fertility evaluation was 35-fold higher than the prevalence in the general male population., (Copyright © 2021. Published by Elsevier Inc.)

Hyperprolactinemia, defined by a level of serum prolactin above the standard upper limit of normal range, is a common finding in clinical practice and prolactinomas are the main pathological cause. Prolactinomas lead to signs and symptoms of hormone oversecretion, such as galactorrhea and hypogonadism, as well as symptoms of mass effect, including visual impairment, headaches and intracranial hypertension. Diagnosis involves prolactin measurement and sellar imaging, but several pitfalls are involved in this evaluation, which may difficult the proper management. Treatment is medical in the majority of cases, consisting of dopamine agonists, which present high response rates, with a very favorable safety profile. Major adverse effects that should be monitored consist of cardiac valvulopathy and impulse control disorders. Other treatment options include surgery and radiotherapy. Temozolomide may be used for aggressive or malignant carcinomas. Finally, pregnancy outcomes are similar to general population even when dopamine agonist treatment is maintained., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Microprolactinomas are currently treated with dopamine agonists. Outcome information on microprolactinoma patients treated by surgery is limited. This study reports the first large series of consecutive non-invasive microprolactinoma patients treated by pituitary surgery and evaluates the efficiency and safety of this treatment., Design: Follow-up of a cohort of consecutive patients treated by surgery., Methods: Between January 2008 and October 2020, 114 adult patients with pure microprolactinomas were operated on in a single tertiary expert neurosurgical department, using an endoscopic endonasal transsphenoidal approach. Eligible patients presented with a microprolactinoma with no obvious cavernous invasion on MRI. Prolactin was assayed before and after surgery. Disease-free survival was modeled using Kaplan-Meier representation. A cox regression model was used to predict remission., Results: Median follow-up was 18.2 months (range: 2.8-155). In this cohort, 14/114 (12%) patients were not cured by surgery, including ten early surgical failures and four late relapses occurring 37.4 months (33-41.8) after surgery. From Kaplan-Meier estimates, 1-year and 5-year disease free survival was 90.9% (95% CI: 85.6-96.4%) and 81% (95% CI: 71.2-92.1%) respectively. The preoperative prolactinemia was the only significant preoperative predictive factor for remission (P < 0.05). No severe complication was reported, with no anterior pituitary deficiency after surgery, one diabetes insipidus, and one postoperative cerebrospinal fluid leakage properly treated by muscle plasty., Conclusions: In well-selected microprolactinoma patients, pituitary surgery performed by an expert neurosurgical team is a valid first-line alternative treatment to dopamine agonists.

The prevalence of hyperprolactinemia in postmenopausal women is unknown and has been estimated as infrequent by many studies. Prolactinomas found after menopause are usually macroadenomas and remain unrecognized for a long time due to atypical clinical signs or their absence. The growth potential of prolactinomas persists after menopause, most of them are invasive and accompanied by high prolactin levels. Treatment with dopamine agonists is usually long-term, the goals of which are to reduce tumor size, normalize prolactin levels and the negative effects of hyperprolactinemia. Treatment with cabergoline makes it possible to achieve remission of the disease in the first years after discontinuation, however, the proportion of relapses in postmenopausal women increases 5 years after discontinuation of the drug. Remission of prolactinomas is not evident in postmenopausal women. The modern management of patients with prolactinoma and/or hyperprolactinemia does not have clear positions in the postmenopausal period. Controversial issues remain: an ambiguous relationship between prolactin levels and breast cancer, there are no convincing conclusions on the improvement of bone mineral density and/or a decrease in the risk of fractures with normalization of prolactin levels, there are no data on metabolic parameters after the end of treatment with dopamine agonists, conflicting information about the relationship of prolactin levels and the severity of the manifold manifestations of the climacteric syndrome. The use of estrogen-progestin drugs in women with hyperprolactinemia/prolactinomas is also not well understood. Thus, the problem of hyperprolactinemia in the perimenopausal and postmenopausal period is underestimated and requires additional research, as well as the development of diagnostic and therapeutic strategies for potential benefits in terms of weight loss, improving insulin sensitivity, reducing the risk of fractures, maintaining sexuality and psycho-emotional well-being.

Background: First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal remission rates are approximately 34%. Therefore, many patients require prolonged DA treatment, while side effects negatively impact health-related quality of life (HRQoL). Endoscopic transsphenoidal resection is reserved for patients with severe side effects, or with DA-resistant prolactinoma. Surgery has a good safety profile and high probability of remission and may thus deserve a more prominent place in prolactinoma treatment. The hypothesis for this study is that early or upfront surgical resection is superior to DA treatment both in terms of HRQoL and remission rate in patients with a non-invasive prolactinoma of limited size., Methods: We present a combined randomised clinical trial and observational cohort study design, which comprises three unblinded randomised controlled trials (RCTs; PRolaCT-1, PRolaCT-2, PRolaCT-3), and an observational study arm (PRolaCT-O) that compare neurosurgical counselling, and potential subsequent endoscopic transsphenoidal adenoma resection, with current standard care. Patients with a non-invasive prolactinoma (< 25 mm) will be eligible for one of three RCTs based on the duration of pre-treatment with DAs: PRolaCT-1: newly diagnosed, treatment-naïve patients; PRolaCT-2: patients with limited duration of DA treatment (4-6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for > 2 years. PRolaCT-O will include patients who decline randomisation, due to e.g. a clear treatment preference. Primary outcomes are disease remission after 36 months and HRQoL after 12 months., Discussion: Early or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three RCTs and an observational cohort study. Within the three RCTs, patients will be randomised between neurosurgical counselling and standard care. The observational study arm will recruit patients who refuse randomisation and have a pronounced treatment preference. PRolaCT will collect randomised and observational data, which may facilitate a more individually tailored practice of evidence-based medicine., Trial Registration: US National Library of Medicine registry (ClinicalTrials.gov) NCT04107480 . Registered on 27 September 2019, registered retrospectively (by 2 months)., (© 2021. The Author(s).)

Objective: Transsphenoidal surgery (TSS) is mainly indicated in prolactinomas when dopamine agonist treatment fails. However, there is no established early predictor of cabergoline (CBG) response. The present study was aimed to identify predictors of CBG resistance in order to select patients who may benefit from early TSS., Design: Retrospective longitudinal study., Methods: We reviewed the medical record of patients diagnosed with prolactinoma after 2010. Inclusion criteria: macroprolactinomas under CBG treatment with serial prolactin levels and MRI before treatment and 3 and 12 months afterwards. The main outcome was tumour size shrinkage ≥ 50% (using the two largest diameters in sagittal view) after 12 months of CBG (TS&#95;50). The capacity of the most important clinical and biochemical variables in predicting the main outcome was examined., Results: A total of 185 prolactinomas where included: 124 (67.0%) were microadenomas and 61 (33.0%) were macroadenomas of which 27 patients meet de inclusion criteria; median age (42.5 years; (IQR: 28.0)). The median follow-up was (67.5 months; (IQR: 30.2)). Ten patients (37.0%) underwent surgery after more than 1 year of CBG. The volume reduction at the first MRI (3-4 months) was the unique valuable predictor: (OR: 1.16 (95% CI: 1.02-1.32)) of TS&#95;50. A tumour volume shrinkage of ≥ 30% in the first 3-4 months of CBG therapy predicts TS&#95;50 with an AUC (0.95 (CI: 0.76-0.99))., Conclusion: Tumour shrinkage in the first 3-4 months after starting treatment with CBG is a good tool for predicting the long-term response and can help clinicians to take more appropriated and personalized decisions.

Most prolactinomas are diagnosed in women of reproductive age and are generally microadenomas. Prolactinomas diagnosed in postmenopausal women are less common and are not usually associated with the typical syndrome induced by prolactin excess, including infertility and oligo-amenorrhea. This implies that the diagnosis of prolactinomas after menopause may be delayed and require greater clinical effort. Limited data are available on the management and prognosis of prolactinomas in postmenopausal women. However, the physiologic decline of prolactin levels during menopause and the lack of fertility concerns, which represent specific indications for medical treatment with dopamine agonists, might require a careful reassessment of therapeutic management in such patients. Postmenopausal women with microprolactinoma may be successfully withdrawn from medical therapy with dopamine agonists, whereas in those with macroprolactinomas greater caution is advisable before dopamine agonists are discontinued, considering the potential, although rare, tumor enlargement. This review focuses on the diagnostic challenges and therapeutic management of prolactinomas in postmenopausal women., (Copyright © 2021. Published by Elsevier B.V.)

Rationale: Multiple endocrine neoplasia type 1 (MEN1) is a rare tumor syndrome with an autosomal dominant inheritance, and genetic testing for MEN1 gene is important for both affected individuals and their relatives. We present a 2-person family affected by a germline c.1546dupC MEN1 mutation, and one of them had a full-spectrum of MEN-related endocrine tumors., Patient Concerns: A female patient aged 32 years presented with jejunal ulcer perforation due to gastrinoma., Diagnoses: We conducted genetic analysis and extensive biochemical/radiological evaluation for detecting other endocrine tumors. Multiple pancreatic neuroendocrine tumors (NETs), prolactinoma and primary hyperparathyroidism were diagnosed, and a frame-shift mutation, NM&#95;130799.1:c.1546dupC (p.Arg516Profs∗15), was detected. One daughter of the proband, aged 12 years, had the same mutation for MEN1., Intervention: She underwent pancreatic surgery for pancreatic NETs and total parathyroidectomy for primary hyperparathyroidism., Outcomes: After pancreatic surgery, long-term symptoms of epigastric soreness, acid belching, sweating, and palpitation in fasting were improved. Hypercalcemia was improved after parathyroidectomy and she was supplemented with oral calcium and vitamin D. Her daughter showed normal biochemical surveillance until 15 years of age., Lessons: We report 2 people in a family affected by MEN1 with the heterozygous germline c.1546dupC mutation, a variant that should be surveilled for early development of full-blown MEN1-associated endocrine tumors., Competing Interests: Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

This article describes a clinical case of prolactinoma, the onset of which was diagnosed after long-term use of eglonil, after the appearance of such side effects as galactorrhea. This clinical case is a unique one because of the peculiarities of diagnostic search. The first complaints of the patient were anxiety and fear, fatigue, frequent mood swings, memory disoders. She was examined by a family physician and prescribed eglonil (sulpiride) 200mg for 7 days. Because of the positive effect the patient decided on her own to continue treatment for another several weeks. But suddenly she revealed a leakage of milk from the mammary glands. The family physician assessed galactorrhea as a side effect of long-term use of eglonil, and cancelled this prescription. Simultaneously the family doctor canceled COCs, that the patient used for the last several years, because of pregnancy planning. But three months later the mensis didn't occur. The menstrual cycle did not resume and pregnancy did not occur even 6 months later. Thus the doctor started to perform complete examination of the patient. Unfortunately, during the diagnostic search the patient rejected to do the contrast and primarily was performed MRI without contrast. The doctor revealed abnormal prolactin level - 423 ng/ml (normal range <25 ng/ml). Finally MRI of the pitutary including dynamic contrast was done. It has demonstrated an 8 x 11 mm mass in pituitary gland. The patient was prescribed conservative treatment according to the protocol. As a result, subsequent monthly control laboratory tests of prolactin levels in blood indicated gradual decrease of its level. Thus the first symptoms of prolactinoma may be atypical and can be detected only by a detailed survey and observation of the patient. It is also known that the severity of symptoms depends on the size of prolactinomas. Large prolactinomas cause symptoms of central nervous system lesion: headaches, depression, anxiety, irritability, emotional instability but in our clinical case, the prolactinoma was small but manifests with severe symptoms of the central nervous system lesion (according to the results of HADScale and MoCA scale). The presence of concomitant pathology can mask or distort the symptoms of another disease that complicates the diagnosis. On the other hand, treatment of one of the comorbidities and improving its course leads to a reduction in the manifestations of the others.

Purpose: Prolactinoma is a type of pituitary tumour that produces an excessive amount of the hormone prolactin. It is the most common type of hormonally-active pituitary tumour. These tumours can cause ocular complications such as vision loss and visual fields (VF) defect. In this study, we aimed to evaluate the thickness of chorioretinal layers in patients with prolactinoma., Methods: We enrolled 63 eyes of 32 prolactinoma patients and 36 eyes of 18 age and gender-matched healthy controls. All participants underwent complete hormonal and ophthalmological examination, including spectral-domain optical coherence tomography (SD-OCT) and VF test.The complete biochemical response was defined as serum PRL concentration ≤ 20 ng/mL at the time of evaluation.The seven layers were retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE). The results of prolactinoma patients were compared with the control group., Results: The mean RNFL, GCL, IPL, INL, ONL, and RPE were thinner in prolactinoma patients than the control group (p < 0.05) while OPL was similar between groups (p > 0.05).None of the patients had VF defect.The thickness of retinal layers was similar in patients with and without complete biochemical response (p > 0.05)., Conclusion: To our knowledge, this is the first study that evaluates the thickness of chorioretinal layers in patients with prolactinoma.Most of the layers were thinner than the control group.Therefore, detailed eye assessment should be a routine component of the follow-up visits of prolactinoma patients and further studies related to this condition are required.

Context: Dopamine agonists (DAs) are the first-line therapy for prolactinomas. Although pituitary tumors often do not completely disappear, discontinuing DAs in patients with no visible tumor on magnetic resonance imaging is advised., Objective: To analyze biochemical remission after cabergoline (CAB) withdrawal in patients with visible remnant pituitary tumors., Design: Retrospective cohort study., Setting: Severance Hospital., Subjects: We identified 734 patients with prolactinomas undergoing CAB therapy for at least 12 months from 2005 to 2018. We selected 44 patients with prolactinomas who discontinued CAB with normal prolactin levels; they were receiving a minimal CAB dose but had visible remnant tumors., Results: Median age at diagnosis was 32 (18-58) years, and most patients were women (95.45%). Median treatment duration was 32 (12-120) months. Of 44 patients, 33 continued to have normoprolactinemia, but 11 patients developed hyperprolactinemia after drug withdrawal within 26 (12-97) months. Age, sex, maximal and remnant tumor size, and treatment duration were similar between the groups. The initial prolactin level and chances of cavernous sinus (CS) invasion were higher in the recurrence group. CS invasion at diagnosis was associated with an increased recurrence rate. Although treatment response did not correlate with the initial and final signal intensity assessments, a significant decrease in T2 intensity ratio after 6 months of CAB therapy was observed in the remission group (P = .043)., Conclusion: In patients with visible tumors, the presence of CS invasion at diagnosis may be an unfavorable predictor for biochemical remission after CAB discontinuation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Controversy exists as to whether low-dose cabergoline is associated with clinically significant valvulopathy. Few studies examine hard cardiac endpoint data, most relying on echocardiographic findings., Objectives: To determine the prevalence of valve surgery or heart failure in patients taking cabergoline for prolactinoma against a matched nonexposed population., Design: Population-based cohort study based on North East London primary care records., Methods: Data were drawn from ~1.5 million patients' primary care records. We identified 646 patients taking cabergoline for >6 months for prolactinoma. These were matched to up to 5 control individuals matched for age, gender, ethnicity, location, diabetes, hypertension, ischemic heart disease, and smoking status. Cumulative doses/durations of treatment were calculated. Cardiac endpoints were defined as cardiac valve surgery or heart failure diagnosis (either diagnostic code or prescription code for associated medications)., Results: A total of 18 (2.8%) cabergoline-treated patients and 62 (2.33%) controls reached a cardiac endpoint. Median cumulative cabergoline dose was 56 mg (interquartile range [IQR] 27-123). Median treatment duration was 27 months (IQR 15-46). Median weekly dose was 2.1 mg. Neither univariate nor multivariate analysis demonstrated a significant association between cabergoline treatment at any cumulative dosage/duration and an increased incidence of cardiac endpoints. In a matched analysis, the relative risk for cardiac complications in the cabergoline-treated group was 0.78 (95% CI, 0.41-1.48; P = 0.446). Reanalysis of echocardiograms for 6/18 affected cabergoline-treated patients showed no evidence of ergot-derived drug valvulopathy., Conclusions: The data did not support an association between clinically significant valvulopathy and low-dose cabergoline treatment and provide further evidence for a reduction in frequency of surveillance echocardiography., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Prolactinoma is the most common cause of pituitary tumours. Current medical guidelines recommend dopamine agonists (cabergoline or bromocriptine) as the initial therapy for prolactinoma. However, surgical removal can also be considered in selected cases, such as patients with macroadenomas with local complications (bleeding or optic chiasm pressure) or those not responding to medical treatment., Methods: The present retrospective study included patients with prolactinomas (n=43; female, 24; male, 19) who were primarily managed with medical (n=32) or surgical (n=11) treatment., Results: Macroadenoma (n=29.67%) was commonly detected in both genders (female, 54%; male, 84%). Moreover, the mean pre-treatment prolactin levels were similar in both genders (female, 683.3 ± 1347 ng/mL; male, 685.4 ± 805 ng/mL; p=0.226). Surgically treated patients had a greater reduction in tumour size (27.7 ± 17.9 mm pre-treatment vs. 8.72 ± 14.2 mm post-treatment) than non-surgically treated ones (12.5 ± 7.5 mm pre-treatment vs. 4.1 ± 4.2 mm post-treatment; p=0.00). However, the decrease in prolactin levels was similar between the two patient groups (p=0.108). During the follow-up period (10.6 ± 7.0 years), the average cabergoline dose of the patients was 1.42 ± 1.47 mcg/week., Conclusions: Although a surgical approach was considered for selected cases of prolactinoma, the average dose used for medical treatment was highly inadequate for the patients in the present study., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Myasthenia gravis (MG) is a rare and potentially dangerous autoimmune condition, which affects the acetylcholine receptors at the neuromuscular junction of skeletal muscle. MG's diverse symptomatology may readily masquerade as other neurological conditions, posing a diagnostic challenge to clinicians. We describe a 24-year old man who presented to the emergency department with a new onset internuclear ophthalmoplegia. After a series of investigations, we eventually arrived at a diagnosis of MG with pseudointernuclear ophthalmoplegia with an incidentally detected prolactinoma. We explore the literature regarding the pathophysiology of pseudointernuclear ophthalmoplegia, the link between prolactin and autoimmunity and the association between prolactinoma and MG., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Withdrawal of dopamine agonist (DA) therapy in patients with prolactinoma who are controlled by a small dose of medication is recommended by several guidelines. So far, the likelihood of reaching withdrawal conditions based on baseline characteristics remains uncertain., Methods: We retrospectively examined early clinical, radiological, or biochemical features that may predict the likelihood of reaching withdrawal conditions in prolactinoma patients. Data were obtained in a single academic medical center in the United States from patients seen between 2000 and 2018. Using multiple logistic regression, we compared patients who reached withdrawal conditions with those who did not., Results: Of 213 patients, 78 (36.6%) reached withdrawal conditions after at least 2 years of DA treatment. Initial maximal tumor diameter was significantly smaller in those who reached withdrawal conditions than in those who did not. Percent prolactin change at the first check from initiation of DA therapy and parasellar invasiveness were predictors of reaching withdrawal conditions. With constant independent variables, there was a 7% increase in odds for reaching withdrawal conditions for every 1% decrease in percent prolactin change at first check after DA therapy start (P = 0.0000). Parasellar invasion decreased the odds of reaching withdrawal conditions by 84% (P = 0.0000)., Conclusions: DA remains a potential life-long treatment modality for most prolactinoma patients. Patients with parasellar invasiveness and low prolactin percent change from baseline to first prolactin check are more likely to require long-term treatment., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)