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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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2024. The Author(s).)

Objective: Transsphenoidal surgery for lactotroph pituitary neuroendocrine tumor (PitNET) lowers serum prolactin concentrations, occasionally below the normal range. However, the clinical significance of postoperative hypoprolactinemia is still unclear. In this study, we retrospectively reviewed the female patients with lactotroph PitNET who were treated with transsphenoidal surgery to elucidate the influence of postoperative hypoprolactinemia on regular menstruation restoration and endocrinological remission., Results: The serum prolactin levels in all thirty three participating females had decreased following surgery. Serum prolactin levels in seven patients had decreased below the lower limit of normal ranges (hypoproactinemia group) and in the remaining twenty six patients, it was within the normal range (non-hypoproractinemia group). In hypoprolactinemia group, regular menstruation was restored in all patients with only lactotroph axis deficiency. Nine patients from the non-hypoprolactinemia group experienced re-elevation of serum prolactin concentration (27%). No patient in hypoprolactinemia group experienced the relapse of hyperprolactinemia. These data suggest that early postoperative hypoprolactinemia after transsphenoidal surgery for lactotroph PitNET is not only a good predictive factor for endocrinological remission but also no unfavorable effects on regular menstruation restoration., (© 2024. The Author(s).)

Purpose: Data regarding the presence of a prolactin (PRL) threshold above which a pituitary magnetic resonance imaging (MRI) is mandatory in patients with hyperprolactinemia (hyperPRL) are controversial and derived primarily from studies focused on female populations. Aim of our study was to evaluate in a cohort of patients of both sexes with confirmed hyperPRL, the possible correlation between PRL values and the presence of pituitary abnormalities., Methods: We retrospectively analyzed data from patients who underwent serial PRL sampling at our Division between January 2015 and December 2022. Patients diagnosed with monomeric hyperPRL at serial sampling and with subsequent contrast-enhanced MRI results available for the pituitary region were included in the study. Exclusion criteria were prior pituitary disease, severe renal insufficiency, liver cirrhosis, uncompensated primary hypothyroidism and ongoing therapy with hyperprolactinemic drugs. Physiological causes of hyperPRL were also ruled out., Results: Out of the 1253 patients who underwent serial PRL sampling, 139 patients (101 women and 38 men) met the inclusion criteria: 106 (76.3%) patients had some form of pituitary disease, with microlesions observed in 69.8%, macrolesions in 25.5% and other findings in 4.7% of subjects. PRL values showed a modest accuracy in predicting the presence of a pituitary abnormality and the best cut-offs identified were >25 µg/L (AUC 0.767, p = 0.003) and >44.2 µg/L (AUC 0.697, p < 0.001) in men and women, respectively; however, if only patients with PRL values > 500 µg/L were excluded from the analysis, as they were already supposed to harbor a macroprolactinoma, PRL levels were not able to predict the presence of a macrolesion neither in men nor women., Conclusion: Given the high prevalence of pituitary abnormalities in patients of both sexes with hyperPRL at serial sampling, performing a pituitary imaging in all cases of hyperPRL, even if mild, appears to be a cautious choice., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest: none to declare.

Prolactinomas (PRLomas) constitute approximately half of all pituitary adenomas and approximately one-fifth of them are diagnosed in males. The clinical presentation of PRLomas results from direct prolactin (PRL) action, duration and severity of hyperprolactinemia, and tumor mass effect. Male PRLomas, compared to females, tend to be larger and more invasive, are associated with higher PRL concentration at diagnosis, present higher proliferative potential, are more frequently resistant to standard pharmacotherapy, and thus may require multimodal approach, including surgical resection, radiotherapy, and alternative medical agents. Therefore, the management of PRLomas in men is challenging in many cases. Additionally, hyperprolactinemia is associated with a significant negative impact on men's health, including sexual function and fertility potential, bone health, cardiovascular and metabolic complications, leading to decreased quality of life. In this review, we highlight the differences in pathogenesis, clinical presentation and treatment of PRLomas concerning the male sex., 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 © 2024 Dzialach, Sobolewska, Zak, Respondek and Witek.)

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.

Context: Treatment of hyperprolactinemia with ergoline dopamine agonists (DAs) can be complicated by intolerance and resistance., Objective: This study examines the efficacy and tolerability of the nonergot DA ropinirole for the long-term treatment of hyperprolactinemia., Methods: Twelve hyperprolactinemic women were treated with ropinirole in a 6-month, open-label, dose-escalation trial; 7 of the 12 continued treatment in an extension study for up to 17 months. Ropinirole doses were uptitrated to achieve normal prolactin (PRL) levels, restore menses, and eliminate galactorrhea., Results: Two of the 12 participants were DA naive; 6 of 12 were ergot DA intolerant; and 1 of 12 had known ergot DA resistance. Baseline PRL levels were 126.2 ± 41.4 ng/mL (SEM). Ropinirole was uptitrated from 0.125 to 0.25 mg/h to a median total daily dose (TDD) of 2 mg/d (1-4 mg/d [interquartile range]). PRL normalization was achieved in 50% of the participants (5 with microadenomas and 1 with idiopathic hyperprolactinemia) at a median effective TDD of 1 mg/d. Of the patients achieving PRL normalization, 83% were ergot DA intolerant. A persistent partial biochemical response (PRL reduction >50% from baseline) was achieved in 17% of the participants. During treatment, menses resumed in 67% of amenorrheic patients; galactorrhea resolved in 67%. Mild adverse effects were reported in 92% of participants; however, ropinirole was not discontinued because of intolerance even among the 50% of individuals with a prior history of ergot DA intolerance and resultant medication discontinuation., Conclusion: These data demonstrate the efficacy and tolerability of ropinirole for the treatment of hyperprolactinemia in patients with microprolactinomas and idiopathic hyperprolactinemia and suggest ropinirole may represent a novel therapeutic alternative for treating hyperprolactinemic disorders in patients with ergot DA intolerance., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The linkage between prolactin (PRL) and systemic lupus erythematosus (SLE) is still vague. Determination of serum levels of prolactin to reveal its role in patients with SLE is the aim of the study., Methods: This is a case-control study performed on 40 children with SLE and 40 age- and sex-matched controls. Cases were further subdivided according to disease activity into mild, moderate, and severe groups using the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score. Serum prolactin levels were assayed by ELISA (enzyme-linked immunosorbent assay)., Results: prolactin level was significantly higher in SLE patients (17.3 ± 6.6 µg/L) than in controls (13.5 ± 5.3 µg/L) (P value = 0.005). Although the prolactin level was highest in severe cases (19.3 ± 7.7 µg/L), followed by moderate cases (17.0 ± 5.3 µg/L), and lowest in mild cases (14.0 ± 6.2 µg/L), the variance between the 3 groups was not statistically significant (P value = 0.212). A significant positive correlation between prolactin level and SLEDAI score was detected (r = 0.368) (P value = 0.019). Hyperprolactinemia was found in 8 patients (20%) but not in controls; 4 out of 8 patients with hyperprolactinemia (50%) showed neurological manifestations compared to only 3 out of 32 patients with a normal prolactin level (9.4%) (P value = 0.007)., Conclusion: A relationship between serum prolactin levels and juvenile SLE disease was detected. Neurological manifestations were more prevalent among SLE patients with hyperprolactinemia., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: The aim of this study was to investigate the association between intraoperative intrasellar pressure (ISP) and pre- and postoperative endocrine disturbances with focus on hyperprolactinemia and hypopituitarism in patients with pituitary tumors., Methods: The study is a consecutive, retrospective study with ISP collected prospectively. One hundred patients operated with transsphenoidal surgery due to a pituitary tumor, who had their ISP measured intraoperatively, were included. Data on patient endocrine status preoperatively and from 3-month postoperative follow-up were collected from medical records., Results: The risk of preoperative hyperprolactinemia in patients with nonprolactinoma pituitary tumors increased with ISP (unit odds ratio 1.067, n = 70) (P = 0.041). Preoperative hyperprolactinemia was normalized at 3 months after surgery. Mean ISP was higher in patients with preoperative thyroid-stimulating hormone (TSH) deficiency (25.3 ± 9.2 mmHg, n = 37) than in patients with intact thyroid axis (21.6 ± 7.2 mmHg, n = 50) (P = 0.041). No significant difference in ISP was found between patients with and without adrenocorticotropic hormone(ACTH) deficiency. No association was found between ISP and postoperative hypopituitarism at 3 months after surgery., Conclusions: In patients with pituitary tumors, preoperative hypothyroidism and hyperprolactinemia may be associated with higher ISP. This is in line with the theory of pituitary stalk compression, suggested to be mediated by an elevated ISP. ISP does not predict the risk of postoperative hypopituitarism 3 months after surgical treatment., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

Objective: Hyperprolactinemia (HPRL) and polycystic ovary syndrome (PCOS) are common causes of infertility in women of reproductive age. A pituitary adenoma (PA) is the most common type of brain tumor that causes HPRL. In the neurosurgical field, the co-existence of PA and PCOS is not common. However, neurosurgeons often treat patients who are referred from gynecology. Because most of these patients are young and reproductive-aged, it is difficult for a neurosurgeon to come up with a treatment plan alone. In this study, we investigated the prevalence of PAs in PCOS patients, the cutoff prolactin (PRL) level to detect PAs, and the treatment strategy, then assessed the relationship between these diseases via a literature review. Methods: Medical records from November 2009 to March 2020 were reviewed at our institute. A total of 657 PCOS patients were enrolled. Initial prolactin levels were investigated and hyperprolactinemic patients were selected. As a result of sella magnetic resonance imaging (MRI), patients were divided into 2 groups of those with hyperprolactinemia but without PAs (group A) and those with both hyperprolactinemia and PAs (group B), respectively. We then compared and analyzed each group to find the characteristics and statistical differences. Receiver operating characteristic (ROC) curve analysis was performed to determine a cutoff value of the serum PRL level that could detect PAs in hyperprolactinemic PCOS patients. Results: Of 657 patients diagnosed with PCOS, 76 patients had hyperprolactinemia (76/657, 11.6%). Sella MRI was performed in 56 patients, excluding 20 patients for various reasons. Patients in groups A and B numbered 43 and 13, respectively, and the mean serum prolactin level significantly differed between the groups (39.89 ± 41.64 vs. 108.59 ± 60.70 ng/mL, P < 0.001). Based on the ROC curve analysis of the prolactin threshold level for predicting PAs in PCOS patients, the area under the ROC curve was 0.853 (95% confidence interval, 0.733-0.934; P < 0.001), and the sensitivity and specificity were 76.9% and 86.1%, respectively. Ultimately, the cutoff value for prolactin level was 52.9 ng/mL. Conclusion: PCOS and hyperprolactinemia are common causes of infertility in reproductive-age women. PCOS patients with a PRL level of ≥ 52.9 ng/mL may need to undergo sella MRI for detecting PAs. To help ensure a favorable clinical course for these patients, systematic diagnosis, treatment, and follow-up plan should be established. Therefore, a multidisciplinary approach involving both neurosurgery and gynecology is essential., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

A purely intrasellar chordoma is rare among skull base chordomas and is recognized as originating from ectopic embryological notochord located in the sella turcica. In view of its rarity and nonspecific symptoms, clinicians may misdiagnose intrasellar chordoma as pituitary adenoma based on preoperative radiographic images. In this report, we present an intrasellar chordoma that clinically mimicked pituitary macroadenoma with hyperprolactinemia and hypopituitarism and was successfully resected by endoscopic endonasal transsphenoidal surgery. This case demonstrated radiographic features that chordoma should be suspected in sellar lesions. The enlarged sellar with thinned remodeled bone without clival destruction was firstly reminiscent of pituitary adenoma, whereas the very high signal on T2-weighted images and heterogeneous enhancement characteristically suggested chordoma. This rare diagnosis must be considered in the preoperative evaluation of sellar lesions because it can affect how the neurosurgeon prepares for surgery and the surgical goals., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Purpose: To analyse the causes of hyperprolactinaemia in patients with symptoms compatible with hyperprolactinaemia evaluated in a primary care setting., Patients and Methods: A retrospective study of all patients tested for serum prolactin levels between 2019 and 2020 in 20 primary care centres at the Hospital Ramón y Cajal in Madrid. Hyperprolactinaemia is defined as a serum prolactin>19.4ng/ml in men and >26.5ng/ml in women. Aetiology is grouped into physiological (pregnancy, lactation, inadequate venipuncture, macroprolactinaemia), pharmacological, pathological (hypothalamic and/or pituitary diseases, chronic renal failure, primary hypothyroidism), and idiopathic., Results: In 1630 patients tested for serum prolactin, 30.7% (n=501) had hyperprolactinaemia. Of these 501 patients, 89.6% were females. 149 patients were referred to the Endocrinology Department and 164 to the Gynaecology Department. Aetiological diagnosis of hyperprolactinaemia was achieved in 411 out of 501 cases. The most frequent cause of hyperprolactinaemia was pharmacological, in 39.1%. The second more frequent cause was idiopathic (29%) and less common were inadequate venipuncture extraction (13.4%), tumour (8.5%) and macroprolactinaemia (3.9%). Patients with tumoural hyperprolactinaemia presented higher serum prolactin levels (87.0±80.19 vs 49.7±39.62ng/ml, P=0.010). In addition, symptoms, such as galactorrhoea (33.3% vs 16.5%, P=0.018), and headache (25.7% vs 13.3%, P=0.045), were more frequent than in patients of the other aetiological groups., Conclusion: Hyperprolactinaemia is common among patients evaluated in a primary care setting with symptoms of hyperprolactinaemia, but more than 50% of cases are due to pharmacological treatments or improper sample extraction. It is necessary to establish referral protocols to specialised medicine to optimise healthcare resources and avoid unnecessary studies., (Copyright © 2022 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Galactorrhea is the production of breast milk that is not the result of physiologic lactation. Milky nipple discharge within one year of pregnancy and the cessation of breastfeeding is usually physiologic. Galactorrhea is more often the result of hyperprolactinemia caused by medication use or pituitary microadenomas, and less often hypothyroidism, chronic renal failure, cirrhosis, pituitary macroadenomas, hypothalamic lesions, or unidentifiable causes. A pregnancy test should be obtained for premenopausal women who present with galactorrhea. In addition to prolactin and thyroid-stimulating hormone levels, renal function should also be assessed. Medications contributing to hyperprolactinemia should be discontinued if possible. Treatment of galactorrhea is not needed if prolactin and thyroid-stimulating hormone levels are normal and the discharge is not troublesome to the patient. Magnetic resonance imaging of the pituitary gland should be performed if the cause of hyperprolactinemia is unclear after a medication review and laboratory evaluation. Cabergoline is the preferred medication for treatment of hyperprolactinemia. Transsphenoidal surgery may be necessary if prolactin levels do not improve and symptoms persist despite high doses of cabergoline and in patients who cannot tolerate dopamine agonist therapy.

Objective: Clinical paradigms and consensus recommend dopamine agonists (DAs) as the primary treatment for prolactinomas. However, medically treated patients also encounter challenges such as DA resistance, intolerable side effects, and recurrence of hyperprolactinemia after DA withdrawal. Technical advances in transsphenoidal resection, with an endoscopic endonasal approach, have led to improved visualization of tumor, decreased postoperative morbidity, and shortened length of stay. We examined the indications and outcomes in patients with prolactinomas who underwent surgical resection at our center., Methods: A retrospective analysis was performed of 60 consecutive patients with prolactinomas who underwent endoscopic endonasal transsphenoidal resection between August 2010 and July 2019 and were followed by the same multidisciplinary team., Results: Women comprised 73% of surgical cases, and 60% of the tumors were macroadenomas. The most common primary surgical indication was patient preference (26.6%) followed by DA intolerance (25%) and DA failure (18.3% inadequate shrinkage, 15% persistent hyperprolactinemia, 11.7% both). Gross total resection was noted in 83% and length of stay was 1 day in 92% of patients. Early remission (postoperative day 1 normalization of prolactin off DA therapy) was seen in 71% of all patients, 91% of microadenomas, 56% of macroadenomas, 65% of Knosp grade 0-2 macroadenomas, and 75% of macroadenomas operated on with expectation of a cure. Only 3 patients had recurrence, at 4.3, 3.3, and 1.6 years of follow-up, respectively., Conclusions: Endoscopic endonasal resection is a viable option for management of patients with prolactinomas in the setting of a high-volume pituitary center, with minimal postoperative complications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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.)

Background: Prolactin is a hormone of the pituitary gland whose main function is the production of milk. Hyperprolactinemia is defined as an increase in prolactin levels above 25 μg/L in women and 20 μg/L in men. Causes of hyperprolactinemia include pituitary tumors, especially prolactinomas. Hyperprolactinemia can manifest clinically with a variety of symptoms, including galactorrhea and menstrual irregularities in women and erectile dysfunction in men. There are limited data on the epidemiology of hyperprolactinemia in the Middle East region., Objectives: Description of the epidemiology and clinical features of hyperprolactinemia in a cohort from Saudi Arabia., Design: Medical record review SETTING: Tertiary medical center in Riyadh PATIENTS AND METHODS: The study included adult patients with hyperprolactinemia in King Abdulaziz Medical City in Riyadh. The patients were treated in endocrinology clinics from 2015 to 2019. Patients of both sexes older than 14 years were enrolled in the study. Patients with insufficient follow-up were excluded. Data were collected on demographic characteristics, symptoms, prolactin level, cause of high prolactin level, and treatment., Main Outcome Measures: The frequency of different etiologies and symptoms in patients with hyperprolactinemia., Sample Size: 295 patients RESULTS: The majority of patients with hyperprolactinemia were female 256 (86.8%). Hyperprolactinemia was diagnosed more frequently in patients in the age groups 21-30 years (42.6%) and 31-40 years (24.1%). The majority of the study population was obese or overweight: 136 (46.3%) and 74 (25.2%), respectively. Most of the cases were symptomatic (192, 65.1%). In women, the most common symptom was oligomenorrhea (35%). In men, infertility and erectile dysfunction were the most common clinical symptoms (50% and 44.7%, respectively). Idiopathic causes were the most common etiology (108, 36.6%), followed by pituitary adenomas (81, 27.5%). The majority of patients were treated (184,62.4%), with cabergoline being the most commonly used medication (173, 94.0%)., Conclusion: The demographic and clinical presentations and causes of hyperprolactinemia in male and female Saudi patients were similar to that in studies in other populations., Limitations: Single-center retrospective chart review study., Conflict of Interest: None.

Purpose: Hyperprolactinemia in the presence of a sellar lesion can be caused by prolactin secretion from the lesion, or by increased intrasellar pressure/compression of the pituitary stalk ("stalk effect"). The objective of this work was to determine the response to dopamine agonists (DAs) in bona fide prolactinomas presenting with a prolactin range similar to what can be seen in nonhormonal secreting pituitary tumors., Methods: A descriptive study on 68 prolactinomas presenting with prolactin levels between 50 and 200 ng/mL in a tertiary center in the U.S.A. over 22 years. The main outcome was prolactin decrease from diagnosis to follow-up by 2 months from initiation of DA therapy., Results: With a median time to follow-up from starting DA therapy of 5 weeks [IQR:4, 6], the median prolactin check showed normality at 11.85 ng/mL [IQR: 5.1, 29]. The median prolactin percent change was at 87% [IQR:67, 94] by 2 months. The majority (75%) of patients presenting had a 2/3 (67%) prolactin drop by 2 months, with more than 1/4 (25%) having a percent drop >95%., Conclusions: A rapid decline in prolactin level can be seen in prolactinomas upon initiation of DA therapy. This significant prolactin drop restricts the ability to establish a threshold beyond which the diagnosis of prolactinoma could be excluded., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Intracranial germ cell tumors (GCTs) are relatively rare, which account for 0.5% of all primary intracranial neoplasms. Intracranial germinomas most commonly occur in the pineal and suprasellar region, making up the majority of all intracranial GCTs. For its diversified clinical manifestations, the diagnosis is easily confused with other diseases. Here, we present a case of a 19-year-old boy with intracranial germinoma who was preliminarily misdiagnosed as hyperthyroidism for the symptoms of weight loss and thyroid dysfunction., 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 Tian, Wu, Yan and Huang.)

Background: Hyperprolactinaemia refers to increased circulating prolactin and is divided into functional and pathological hyperprolactinaemia. Prolactinoma is the most common cause of severe hyperprolactinaemia. Prolactinomas are rare in children. Treatment outcomes and long-term follow-up data in children are insufficient. Dopamine agonists are the first step in the treatment of prolactinomas. There are no recommendations supported by a high level of evidence regarding the dose and duration of cabergoline treatment., Methods: Patients with hyperprolactinaemia were evaluated for etiological, clinical, and follow-up characteristics. The case files of patients with high prolactin levels who were followed up in our clinic between 2001 and 2019 were reviewed retrospectively., Results: 27 cases (20 female, 7 male) with hyperprolactinemia were detected. The median age of the cases was 15 years (0.3-17.4). Prolactinoma was detected in 40.7% of the cases (n=11). Among these cases, six were macroadenomas. The median prolactin level was 118 ng/mL (34-4340) in those with prolactinoma and 60 ng/mL (22-200) in the hyperprolactinaemia group (p=0.007). In the prolactinoma group, the median age at presentation in macroadenoma cases (13.8 years) was lower than in microadenoma cases (17 years) (p=0.06). There was a negative correlation between prolactin level and height SDS (r=-0.770, p=0.06). In all cases, the median initial cabergoline dose was 0.5 mg/week, and prolactin levels returned to normal within an average of 2.6±2.4 months. Cabergoline treatment achieved a 50% reduction in adenoma size in the first year of treatment without high doses., Conclusions: Prolactinoma consists of an important group among hyperplolactinemia in children. In our study, prolactinoma was detected in 40.7% of children with hyperplolactinemia, and children with prolonged use (over 4 years) tolerated cabergoline well and prolactin levels normalized without high doses. Follow-up is required for relapse after discontinuing the treatment.

Objective: This study aimed to investigate the value of contrast-enhanced 3-dimensional (3D) T2-weighted (T2W) Volume Isotropic Turbo Spin Echo Acquisition (VISTA) sequence in prolactin-secreting pituitary adenoma diagnosis., Methods: We enrolled 158 patients with hyperprolactinemia. Coronal dynamic contrast-enhanced (DCE) T1 spin echo and T2W VISTA sequences were performed. The detection of pituitary microadenomas in 3 imaging groups (DCE magnetic resonance imaging [MRI], VISTA, and DCE MRI + VISTA) were compared using McNemar test and χ2 test., Results: The DCE MRI + VISTA group detected 28 more pituitary microlesions than DCE MRI alone. Among these, 20 lesions were clearly observed on VISTA images but were negative on DCE MRI. The combined sequences showed higher sensitivity (85.3%) and diagnostic accuracy (89.2%) for adenoma detection than any of the sequences alone (P < 0.01). We noted that in 65.7% of the patients with adenoma (46 of 70), a "hypointense rim" was present around the lesion on the VISTA images. Of them, 11 patients underwent surgery. Histopathology confirmed that the "hypointense rim" was a pseudocapsular structure at the edge of the adenoma., Conclusions: For patients with hyperprolactinemia, the 3D T2W VISTA sequence is an important supplement to DCE MRI, because it could improve the detection rate of pituitary microadenomas., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

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.)

Introduction: In spite of the increasing prevalence of polycystic ovary syndrome, there are restricted studies about different features of PCOS. In this study, we evaluate serum prolactin levels in PCOS patients and compare clinical features and hormone levels between patients with hyperprolactinemia and normal levels of prolactin., Methods: Serum prolactin level in 330 PCOS patients were evaluated. If the prolactin levels were normal (equal to or less than 25 ng/ml) the patient was considered normal. If the prolactin levels were >25 ng/ml, then the level was measured by Polyethylene glycol (PEG) precipitation method to detect macroprolactinemia. Furthermore, brain MRI was done in case of hyperprolactinemia to discover pituitary adenoma., Results: Among 330 patients with PCOS, 208 (63.4%) had normal prolactin levels and 122 (37%) patients had hyperprolactinemia. Among hyperprolactinemic patients, 72 (59%) had normal prolactin levels after PEG precipitation and 33 (27%) patients had pituitary adenoma in their brain MRI and 17 (13%) patients were considered as idiopathic hyperprolactinemia with normal MRI. Further, higher levels of LH and LH/FSH ratio and lower estradiol levels were observed in patients with normal prolactin levels. Also, menstrual disorders were more prevalent among patients with pituitary adenoma., Conclusions: Investigating increased level of prolactin in PCOS patients is recommended to detect the causes of hyperprolactinemia, especially macroprolactinemia.

Hyperprolactinemia is a condition of elevated serum prolactin, which usually occurs in women as compared to men. Most patients present to primary care clinics with a history of galactorrhoea, oligomenorrhea, amenorrhoea or infertility. Literature search reveals that there were few idiopathic causes of hyperprolactinemia, which resolved by itself without specific pharmacological or surgical treatment. This case is of a 39-year-old woman presented with amenorrhea for four months after Implanon removal and concomitantly noted to have galactorrhoea for four years without any medical attention. The condition persisted after cessation of breastfeeding. After undergoing several investigations including imaging studies, the underlying cause of hyperprolactinemia was noted to be idiopathic. Due to the unclear cause of its aetiology, this case caused various challenges to the primary care. Exhaustive physiological and pathological causes of hyperprolactinemia have been ruled out. Nevertheless, with adequate treatment, she gained her normal menstrual and resolved galactorrhoea symptoms.

Hyperprolactinemia is a relatively common diagnosis to be expected in an adolescent age group with chronic menstrual disturbances. The present case report documents the efficacy of Ayurvedic management in a 21-year-old female with secretory pituitary microadenoma, which was found to be responsible for menstrual disturbances. The patient, with high prolactin levels with pituitary microadenoma, was subjected to an Ayurvedic management protocol, including Śhamana nasya for 7 days followed by Śhamana Cikitsa for 3 months. Patient follow-up was 6 months in duration. The clinical presentation of this case points towards the diagnosis of Asrgdara in Ayurveda. This is the first such case documented where Ayurveda was used as the intervention in a case of pituitary microadenoma with hyperprolactinemia, resulting in the complete absence of microadenoma and normalization of the prolactin level.

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.)

Introduction: Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists (DAs) in neurological as well as endocrine conditions. Few studies have evaluated the neuropsychological effect of DAs in hyperprolactinemic patients, and these have reported a relationship between DAs and ICDs. Our objective was to screen for ICD symptoms in individuals with DA-treated endocrine conditions., Materials and Methods: A cross-sectional analysis was conducted on 132 patients with pituitary disorders treated with DAs (DA exposed), as well as 58 patients with pituitary disorders and no history of DA exposure (non-DA exposed). Participants responded to the full version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP)., Results: Compared with the non-DA-exposed group, a higher prevalence of DA-exposed patients tested positive for symptoms of any ICD or related behavior (52% vs. 31%, p < 0.01), any ICD (46% vs. 24%, p < 0.01), any related behavior (31% vs. 17%, p < 0.05), compulsive sexual behavior (27% vs. 14%, p < 0.04), and punding (20% vs. 7%, p < 0.02) by QUIP. On univariate analysis, DA treatment was associated with a two- to threefold increased risk of any ICD or related behavior [odds ratio (OR) 2.43] and any ICD (OR 2.70). In a multivariate analysis, independent risk factors for any ICD or related behavior were DA use (adjusted OR 2.22) and age (adjusted OR 6.76). Male gender was predictive of the risk of hypersexuality (adjusted OR 3.82)., Discussion: Despite the QUIP limitations, a clear sign of increased risk of ICDs emerges in individuals with DA-treated pituitary disorders. Our data contribute to the growing evidence of DA-induced ICDs in endocrine conditions., (© 2020. The Author(s).)

Hyperprolactinemia can have different causes: physiological, pharmacological, and pathological. When investigating the etiology of hyperprolactinemia, clinicians need to be aware of several conditions leading to misdiagnosis. The most popular pitfalls are: acute physical and psychological stress, macroprolactin, hook effect, even though antibodies interferences and biotine use have to be considered. A 52-year-old woman was referred to Endocrinology clinic for oligomenorrhoea and headache. She worked as a butcher. Hormonal evaluation showed very high PRL (305 ng/ml, reference interval: <24 ng/ml) measured with the ECLIA immunoassay analyzer Elecsys 170. The patient's pituitary MRI was normal and macroprolactin was normal. Hormonal workup showed LH: 71.5 mU/ml (2-10.9 mU/ml), FSH: 111.4 mU/ml (3.9-8.8 mU/ml), Estradiol: 110.7 pg/mL (27-122 pg/ml). Since an interference was suspected, the sample was sent to another laboratory using a different assay. After antibody blocking tubes treatment (Heterophilic Blocking Tube, Scantibodies) PRL was 28.8 ng/ml (reference interval < 29.2 ng/ml). Analytical interference should be suspected when assay results are not consistent with the clinical picture. Endogenous antibodies (EA) include heterophile, human anti-animal, autoimmune and other nonspecific antibodies, and rheumatoid factors, that have structural similarities and can cross-react with the antibodies employed by the immunoassay, causing hyperprolactinemia misdiagnosis. The patient's job (butcher), led us to suspect the presence of anti-animal antibodies. Clinicians should also carefully investigate the use of supplements. Biotin can falsely increase hormone concentration in competitive assays. Many clinicians are still not informed about these pitfalls that are not mentioned in some recent reviews on PRL measurement.

Purpose: Men with mild to moderate hyperprolactinemia rarely present with normal pituitary on MRI with no visible adenoma, a condition entitled also "idiopathic hyperprolactinemia" or "non-tumoral hyperprolactinemia". We have characterized a cohort of hyperprolactinemic men with normal pituitary imaging., Design: We have identified 13 men with true hyperprolactinemia and normal pituitary MRI. Baseline clinical and hormonal characteristics and response to medical treatment were retrospectively retrieved from medical records., Results: Mean age at diagnosis was 51 ± 16 years (range, 20-77); mean serum prolactin level at presentation was 91 ng/ml (range, 28-264), eight men presented with low baseline testosterone. Initial complaints leading to diagnosis included sexual dysfunction in ten men and gynecomastia in five. All patients were treated with cabergoline, except for one who was given bromocriptine; none required pituitary surgery. All patients normalized prolactin and testosterone with subsequent clinical improvement reported by most men. Currently, after a mean follow-up of 72 months, ten patients continue treatment with caborgoline (median weekly dose, 0.25 mg), whereas three men discontinued treatment., Conclusions: Men with symptomatic hyperprolactinemia may rarely present with normal pituitary imaging. Medical treatment can lead to hormonal improvement with clinical benefit.

Context: The relationship between the endocrine system and autoimmunity has been recognized for a long time and one of the best examples of autoimmune endocrine disease is autoimmune hypophysitis. A better understanding of autoimmune mechanisms and radiological, biochemical, and immunological developments has given rise to the definition of new autoimmune disorders including autoimmunity-related hypothalamic-pituitary disorders. However, whether hypothalamitis may occur as a distinct entity is still a matter of debate., Evidence Acquisition: Here we describe a 35-year-old woman with growing suprasellar mass, partial empty sella, central diabetes insipidus, hypopituitarism, and hyperprolactinemia., Evidence Synthesis: Histopathologic examination of surgically removed suprasellar mass revealed lymphocytic infiltrate suggestive of an autoimmune disease with hypothalamic involvement. The presence of antihypothalamus antibodies to arginine vasopressin (AVP)-secreting cells (AVPcAb) at high titers and the absence of antipituitary antibodies suggested the diagnosis of isolated hypothalamitis. Some similar conditions have sometimes been reported in the literature but the simultaneous double finding of lymphocytic infiltrate and the presence of AVPcAb so far has never been reported., Conclusions: We think that the hypothalamitis can be considered a new isolated autoimmune disease affecting the hypothalamus while the lymphocytic infundibuloneurohypophysitis can be a consequence of hypothalamitis with subsequent autoimmune involvement of the pituitary. To our knowledge this is the first observation of autoimmune hypothalamic involvement with central diabetes insipidus, partial empty sella, antihypothalamic antibodies and hypopituitarism., (© 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.)

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.)

Hyperprolactinemia is a prevalent endocrine disorder presented in patients with non-functional pituitary adenomas (NFPAs). However, the mechanism involved in hyperprolactinemia in NFPA is not fully illustrated. The current study aims to investigate predictors for hyperprolactinemia in NFPA via analyzing relevant clinical features. Thus, in this study, a cohort of 214 cases with integrated medical records was retrospectively analyzed concerning clinical, pathological, and endocrinological studies before and after surgery.Hyperprolactinemia happened in 93 cases (43.5%). Women (adjust odds ratio [OR] = 3.093; P < .01), age of patients (adjust OR = 0.951; P < .01), and serum free tetraiodothyronine (FT4) level (adjust OR = 0.882; P = .02) were independent predictors for developing preoperative hyperprolactinemia. Tumor size and hypopituitarism had no impact on hyperprolactinemia. During a median follow-up of 43.5 (range, 22-80) months, 83.9% patients with preoperative hyperprolactinemia experienced prolactin (PRL) normalization. Preoperative PRL level (adjusted OR = 1.741, P = .03) was the exclusive predictor for PRL normalization after adjusting for tumor volume, preoperative serum FT4 concentration, and postoperative residual. The PRL normalization rate of patients with lower PRL level (<2.35-fold upper limit of normal range) was 95.2% and decreased to 65.5% for patients with higher PRL level.In conclusion, our results suggest existence of potentially alternative mechanisms underlying hyperprolactinemia in NFPAs, like the discrepancy of sex and age and the negative feedback of FT4. Preoperative PRL is a predictor for postoperative PRL normalization, which is of clinically relevant for postoperative management of NFPAs.

The aim of this study is to assess differences in patient characteristics, tumour characteristics and hormone levels between acromegalic patients with and without hyperprolactinemia. 44 patients of the University Hospital of Brussels, Belgium with acromegaly who were diagnosed between January 2007 and July 2018 were included in this study. Nineteen patients were classified in the hyperprolactinemia group and 25 patients were classified in the normoprolactinemia group. No significant differences between acromegalic patients with and without hyperprolactinemia were found in age at diagnosis, gender, presence of hyperprolactinemia symptoms, insulin-like growth factor 1, growth hormone and testosterone levels, tumour volume, tumour invasiveness, immunohistochemistry of growth hormone and prolactin, Ki-67 index and mitotic index. However, for a cut-off of 10% of prolactin-positive cells, there was a trend towards a higher percentage of prolactin-positive tumours in hyperprolactinemia patients (p=0.054) and higher mean prolactin level in case of positive prolactin immunostaining (p=0.007)). In our study there were no differences in characteristics between acromegaly patients with hyper- and normoprolactinemia. An association between the serum prolactin level and the positivity of prolactin immunohistochemistry of the adenoma tissue was found. The absence of a difference in tumour volume between patients with hyper- and normoprolactinemia suggests that the hyperprolactinemia is likely to be caused by the co-secretion of growth hormone and prolactin by the tumour. Finally, for the first time, the cut-off of 10% of prolactin cells was validated for the diagnosis of somatolactotroph tumours in acromegaly., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Endoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA., Methods: A retrospective review of 601 consecutive patients who underwent ETSS between 2010 and 2018 at one institution was performed. Recovery or development of new hypopituitarism was analyzed in 209 NFPA patients who underwent ETSS., Results: Patients with preoperative endocrine deficits (59.8%) in one or more pituitary axes had larger tumor volumes (P = 0.001) than those without preoperative deficits. Recovery of preoperative pituitary deficit occurred in all four axes, with overall mean recovery of 29.7%. The cortisol axis showed the highest recovery whereas the thyroid axis showed the lowest, with 1-year cumulative recovery rates of 44.3% and 6.1%, respectively. Postoperative hypopituitarism occurred overall in 17.2%, most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Axis-specific predictors of post-operative recovery and deficiency were identified., Conclusions: Dynamic alterations in pituitary hormones were observed in a proportion of patients following ETSS in NFPA patients. Postoperative endocrine vulnerability, recovery, and factors that predicted recovery or loss of endocrine function depended on the hormonal system, necessitating an axis-specific surveillance strategy postoperatively.

An association between prolactinemia with disability, clinical forms, and sex of patients with multiple sclerosis (MS) remains unclear. The aim of this study was to evaluate the association of prolactin with clinical forms and accumulating disability over time in patients with MS. A longitudinal study was carried out with 101 patients with relapsing-remitting MS (RRMS) and 19 with progressive forms of MS (ProgMS). The disability over time, as well as prolactin and ferritin serum levels were evaluated at baseline (T0), 8-month follow-up (T8), and 16-month follow-up. The disability at T0, T8, and T16 was higher among patients with ProgMS than those with RRMS. Prolactin and ferritin levels did not differ over time between both groups. Initially, prolactin was associated with MS disability. After introducing age and sex, the effects of prolactin on disability were no longer significant. Prolactin was associated with age and sex, whereby age was positively associated with disability. In the same way, after introducing age and sex, the effects of diagnosis on prolactin levels, as well as the association between prolactin and ferritin, were no longer significant (P = 0.563 and P = 0.599, respectively). Moreover, 21.6% of the variance in the disability was predicted by age (P < 0.001), and sex (P = 0.049), while prolactin was not significant. In conclusion, the effects of prolactin on the disability and clinical forms of MS patients may be spurious results because those correlations reflect the positive associations of age with the disability and the negative association of age with prolactin.

Background: Antipsychotic medication, stress, gender, and age are factors that influence prolactin levels in patients with psychosis. The aim of the study was to investigate the level of prolactin response to antipsychotic treatment in acute patients, taking into account the total duration of psychosis., Methods and Findings: The study was conducted on 170 acute patients with schizophrenia spectrum disorders and bipolar disorder. Subjects were divided into three subgroups according to the duration of the psychosis (less than 5 years, between 5 and 10 years and more than 10 years of disorder duration). The initial prolactin response under antipsychotic treatment was measured, while the severity of the psychiatric symptoms was assessed with the BPRS (Brief Psychiatric Rating Scale). Hyperprolactinemia was found in 120 (70.6%) patients, amongst which 80 (66.7%) were females and 40 (33.3%) were males. The average increase in prolactinemia was 2.46 times the maximum value in women, and 1.59 times in men. Gender (β = 0.27, p<0.0001), type of antipsychotic medication according to potency of inducing hyperprolactinemia (β = -0.23, p<0.003), and the duration of psychosis over 10 years (β = -0.15, p = 0.04) significantly predicted prolactin levels, when age, diagnosis, antipsychotic category (conventional/atypical/combinations of antipsychotics), and BPRS total scores were controlled for., Conclusions and Relevance: Prolactin levels in patients treated with antipsychotic medication appeared to depend on patients' gender, on the type of antipsychotic medication according to potency of inducing hyperprolactinemia, and on the duration of the psychosis. An increase in prolactin levels was associated with female gender, while the use of prolactin sparing antipsychotics and a duration of psychosis over 10 years were associated with lower prolactin levels., Competing Interests: The authors have declared that no competing interests exist.

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis of small vessels that affect the pituitary gland in less than 1% of cases being exceptionally rare. To describe the clinical, biochemical, radiological findings, treatment, and outcomes of 4 patients with GPA-related hypophysitis. A systematic review of published cases with the same diagnosis is presented as well. A cross-sectional case series of patients with hypophysitis due to GPA from 1981 to 2018 at a third level specialty center. Literature review was performed searching in seven different digital databases for terms "granulomatosis with polyangiitis" and "pituitary gland" or "hypophysitis," including in the analysis all published cases between 1950 and 2019 with a minimum follow-up of 6 months. We found 197 patients with GPA in our institution of whom 4 patients (2.0%) had pituitary involvement. Clinical characteristics and outcomes are described. We also reviewed 7 case series, and 36 case reports describing pituitary dysfunction related to GPA from 1953 to 2019, including the clinical picture of an additional 74 patients. Pituitary dysfunction due to GPA is rare. Treatment is targeted to control systemic manifestations; nevertheless, the outcome of the pituitary function is poor. Central diabetes insipidus, particularly in younger women with other systemic features, should raise suspicion of GPA.Key Points• Involvement of the pituitary gland is an uncommon manifestation in GPA patients. The presence of central diabetes insipidus in the setting of systemic symptoms should prompt its suspicion.• In patients with pituitary involvement due to GPA, affection of other endocrine glands is rare, neither concomitant nor in different times during the disease course. This may arise the hypothesis of a local or regional pathogenesis affection of the gland.• There is no consensus on the best therapy strategy for GPA hypophysitis. Although the use of glucocorticoids with CYC is the most common drug combination, no differences in the outcome of the pituitary function and GPA disease course are seen with other immunosuppressants.• Poor prognosis regarding pituitary function is expected due to possible permanent pituitary tissue damage that results in the need of permanent hormonal replacement.

Objective: Rathke's cleft cysts (RCCs) may have various anatomic, clinical, and radiologic characteristics, which may be related to their differences in texture or consistency. The purpose of the study was to investigate RCCs based on consistency., Methods: We retrospectively reviewed 25 cases of patients with RCCs who underwent endoscopic endonasal transsphenoidal surgery between 2008 and 2018. Cases were divided into 3 types based on cyst consistency: fluid (serous) or type A (n = 4); semi-fluid (mucoid) or type B (n = 17); and non-fluid (caseous) or type C (n = 4). Demographic, clinical, radiologic, and surgical characteristics for each group were analyzed., Results: All type A RCCs (100%) had visual impairment. The mean age (42.8 ± 13 years) and cyst volume (2442.5 ± 533.6 mm 3 ) were higher in these patients. T1-weighted images were hypointense and T2-weighted images were hyperintense on magnetic resonance imaging. Type B RCCs were more frequently encountered (68%). Although headache was the most common (82.3%) symptom, endocrine disorders were also prevalent (52.9%). T1-weighted images were typically isointense or hyperintense on magnetic resonance imaging. Type C RCCs had the youngest patient population (30.3 ± 10.2 years) and T2-weighted images were predominantly hypointense in this group., Conclusions: The proposed novel consistency classification of RCCs will provide a practical tool for more accurately estimating the nature of the pathology, because each type has its own specific characteristics. Furthermore, the new classification of RCCs may aid in planning a consistency-specific surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A 34-year-old woman presented our hospital with complaint of irregular menstruation and abnormal uterine bleeding lasting for a month. After her second parturition at the age of 27, her menstrual cycle had been regular, but it suddenly became irregular at the age of 30. Transvaginal ultrasound revealed the presence of ovarian mass, and the patient underwent diagnostic laparoscopic surgery. Bilateral ovaries temporally shrink after puncture but the size soon resumed. Gonadotropins were almost normal, but estradiol and PRL levels turned out to be elevated, and cabergoline treatment was initiated. After referral to our hospital, we found that the ovaries showed multifollicular appearance. Brain magnetic resonance imaging showed an 18-mm macroadenoma in the suprasellar area. To suppress the secretion of endogenous gonadotropins and estrogen, low-dose estrogen-progestin was prescribed. Surprisingly, the treatment temporarily reduced the size of the ovaries. The patient was referred to a neurosurgeon, and a functioning gonadotroph adenoma was suspected. After the resection of the pituitary tumor, her menstrual cycle became regular, and the size of bilateral ovaries became normal. We also noticed that her ovarian reserve judged by anti-Müllerian hormone had been almost diminished after the surgical treatment, probably reflecting the exhaustion of follicular pool. Women with multifollicular ovaries and elevated estradiol levels may have functioning gonadotroph adenomas, although the level of FSH is relatively normal, and ovarian reserve can be followed by measuring anti-Müllerian hormone.