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The present study focused on Sahiwal cows, a prominent milch breed in tropical India, to correlate udder temperature with physiological markers of stress and inflammation during subclinical mastitis (SCM). The primary goal was to assess the potential of udder infrared thermography for the early detection of SCM under the semi-intensive production. Cows were categorized based on milk somatic cell counts (SCC), with healthy (H) cows having SCC <2 × 10 5  cells/mL and no history of mastitis, and cows with subclinical mastitis (SCM) and initial stages of clinical mastitis (CM) having quarter milk SCC of 2-5 × 10 5 and >5 × 10 5  cells/mL, respectively. Firstly, udder thermograms were analysed for udder skin surface temperature (USST), teat skin surface temperature (TSST), and teat apex temperature (TAT) using Fluke software to determine the optimal site for temperature measurement during intramammary infection. Secondly, milk samples were collected for automatic estimation of compositional changes, electrical conductivity, and pH. Thirdly, milk whey was separated for quantifying stress and inflammatory indicators, including cortisol, prolactin, and acute-phase proteins (APPs): milk amyloid A and milk haptoglobin using bovine-specific ELISA kits. Significant increases (p < 0.01) in USST, TSST, TAT, cortisol, and APPs were observed in SCM and CM compared to healthy cows, while prolactin levels decreased (p < 0.01). The correlation matrix revealed strong positive correlations of SCC with USST (r = 0.84, p < 0.01). In ROC analysis, USST demonstrated cut-off values of 37.74 and 39.58 °C, with accuracy (p < 0.05) of 98% for SCM and 95% for CM, surpassing both TAT and TSST. Therefore, the combination of these non-invasive methods increases the reliability and accuracy of infrared thermography for early detection of SCM, providing valuable insights for the development of a protocol for routine screening and udder health monitoring in indigenous dairy cows., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The harderian gland (HG) is a gland located at the base of the nictating membrane and fills the inferomedial aspect of the orbit in rodents. It is under the influence of the hypothalamic-pituitary-gonadal axis and, because of its hormone receptors, it is a target tissue for prolactin (PRL) and sex steroid hormones (estrogen and progesterone). In humans and murine, the anterior surface of the eyes is protected by a tear film synthesized by glands associated with the eye. In order to understand the endocrine changes caused by hyperprolactinemia in the glands responsible for the formation of the tear film, we used an animal model with metoclopramide-induced hyperprolactinemia (HPRL). Given the evidences that HPRL can lead to a process of cell death and tissue fibrosis, the protein expression of small leucine-rich proteoglycans (SLRPs) was analyzed through immunohistochemistry in the HG of the non- and the pregnant female mice with hyperprolactinemia. The SRLPs are related to collagen fibrillogenesis and they participate in pro-apoptotic signals. Our data revealed that high prolactin levels and changes in steroid hormones (estrogen and progesterone) can lead to an alteration in the amount of collagen, and in the structure of type I and III collagen fibers through changes in the amounts of lumican and decorin, which are responsible for collagen fibrillogenesis. This fact can lead to the impaired functioning of the HG by excessive apoptosis in the HG of the non- and the pregnant female mice with HPRL and especially in the HG of pregnancy-associated hyperprolactinemia., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Domperidone is a dopamine-2 (D2) receptor antagonist that stimulates the release of stored prolactin in the anterior pituitary. It is prescribed off-label in Canada and Australia to promote lactation in prolactin-deficient women. The case of a 43-year-old woman taking a high daily dose of domperidone (160 mg) is described from the InfantRisk Center Human Milk Biorepository. Milk samples were analyzed using a high-performance liquid chromatography-mass spectrometry method, detecting an average domperidone concentration of 7.0 ng/mL (range 6.2 to 8.4 ng/mL). Even at high doses, the transfer of domperidone into breast milk was negligible with a relative infant dose (RID) of 0.05%. The RID estimates the infant's potential exposure to a drug via lactation as a percentage of the weight-adjusted maternal dose. The standard threshold for reasonable infant exposure is an RID of 10%.

Objectives: Macroprolactin cross-reacts in immunoassays for prolactin causing apparent hyperprolactinaemia (macroprolactinaemia) and consequent misdiagnosis and mismanagement of patients., Methods: We determined the prevalence of macroprolactinaemia using prolactin immunoassays with reported "high" (Tosoh) or "low" cross-reactivity (Roche) with macroprolactin. We additionally modelled the effects of increasing the screening threshold on workload and sensitivity in the detection of macroprolactinaemia., Results: A review of routine requests for prolactin received in a 12 month period identified 670 sera with hyperprolactinaemia (Tosoh assay). Treatment with polyethylene glycol (PEG) precipitation demonstrated normal levels of monomeric prolactin in 165 sera (24.6%) indicating macroprolactinaemia. In the macroprolactinaemic cohort, total prolactin levels were lower with the Roche assay (473 ± 132 mU/L; mean ± SD) compared to the Tosoh assay (683 ± 217 mU/L), p < 0.005. The prevalence of macroprolactinaemia was also lower with the Roche assay (6.2%). The number of samples that required screening for macroprolactinaemia fell by 14% when Roche gender specific total prolactin reference limits were applied. Use of a higher screening threshold (700 mU/L) reduced the screening workload considerably (Roche by 45%, Tosoh by 37%) however, the sensitivity of detection of macroprolactinaemia decreased markedly (Roche 90%, Tosoh 59%)., Conclusions: Macroprolactin interferes in both Tosoh and Roche prolactin immunoassays. Use of an assay with a relatively low cross reactivity with macroprolactin, e.g. Roche, will lead to a modest reduction in the screening workload. Increasing the screening threshold above the upper limit of the assay reference interval will also reduce the screening workload but leads to disproportionate increases in the number of cases of macroprolactinaemia which are missed., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Prolactin (PRL) is produced by the pituitary gland and plays a vital role in the production of milk after a baby is born. PRL levels are normally elevated in pregnant and nursing women, and high levels of PRL in the human body cause hyperprolactinemia, infertility, galactorrhea, infrequent or irregular periods, amenorrhea, breast pain, and loss of libido. Accordingly, herein, a novel label-free immunosensor using a bismuth sulfide/polypyrrole (Bi 2 S 3 /PPy)-modified screen-printed electrode (SPE) for the fast and facile detection of the peptide hormone PRL. Bi 2 S 3 nanorods were synthesized via a facile hydrothermal technique, and PPy was prepared by chemical polymerization method. Subsequently, the Bi 2 S 3 /PPy/ SPE was modified with 3-mercaptopropionic acid (MPA) and EDC/NHS. Owing to the cross-linking effect of EDC/NHS, antibody-PRL (anti-PRL) was firmly stabilized on the modified SPE surface. These layer-by-layer modifications enhanced the conducting properties, anti-PRL loading capacity, and sensitivity of the developed immunosensor. Under optimized conditions, the PRL immunosensor demonstrated a broad linear range of approximately 1-250 ng/mL, a low detection limit of approximately 0.130 ng/mL (3 × SD/b), good specificity, reproducibility, and stability. PRL was successfully evaluated in human and mouse serum samples, and the corresponding outcomes were compared with those of the electrochemical and ELISA methods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Materials and Methods: In this cross-sectional case control study, the serum level of LH, FSH, and prolactin of 40 women with lichen planus who have been referred to Shiraz Dental Faculty, Oral and Maxillofacial Disease Department during 2018-2019 has been evaluated in comparison to 40 healthy controls. Data were analyzed by SPSS version 18. Two-way ANOVA and Mann-Whitney test were used for data analysis., Results: The mean serum level of FSH and LH was significantly higher in OLP patients while this difference was not reported for prolactin. Only FSH mean serum level was significantly higher in nonmenopausal OLP patients. The distribution of prolactin and FSH hormones' serum level was in normal range., Conclusions: The high serum level of FSH and LH can affect OLP pathogenesis by estrogen and progesterone modulation., Competing Interests: There is no conflict of interest to declare., (Copyright © 2021 Fatemeh Lavaee et al.)

Background: Macroprolactin is responsible for pseudohyperprolactinemia and is a common pitfall of the prolactin immunoassay. We aimed to determine the frequency of macroprolactinemia in Chinese hyperprolactinemic patients using monomeric prolactin discriminated by precipitation with polyethylene glycol (PEG)., Methods: Post-PEG monomeric prolactin gender-specific reference intervals were established for the Elecsys immunoassay method (Roche Diagnostics) using sera from healthy female (n = 120) and male (n = 120) donors. The reference intervals were validated using 20 macroprolactinemic (as assessed by gel filtration chromatography (GFC)) sera samples, and presence of monomeric prolactin was discriminated by GFC. Patients with high total prolactin were then screened by PEG precipitation to analyze macroprolactin. The demographic and biochemical details of patients with true hyperprolactinemia and macroprolactinemia were compared., Results: Reference intervals for monomeric prolactin in females and males were 3.4-18.5 and 2.7-13.1 ng/mL, respectively. Among 1140 hyperprolactinemic patients, macroprolactinemia was identified in 261 (22.9 %) patients while the other 879 (77.1 %) patients were diagnosed with true hyperprolactinemia. Menstrual disturbances were the most common clinical feature in both groups. Galactorrhea, amenorrhea, and visual disturbances occurred more frequently in true hyperprolactinemic patients (P < 0.05)., Conclusions: The prevalence of macroprolactin in Chinese patients with hyperprolactinemia was described for the first time. Monomeric prolactin concentration, along with a reference interval screening with PEG precipitation, provides a diagnostic approach for hyperprolactinemia with improved accuracy., (© 2021. The Author(s).)

Sexual function is essential for species survival. Melanocortin, progesterone, and estrogen can improve sexual function and they are modulated by adiponectin hormone which can be increased by Turmeric. In various studies shows Turmeric ability that is easily accessible to increase serum adiponectin levels. Therefore, the researchers decided to conduct a study to determine the effect of turmeric on serum adiponectin levels, sexual behavior, and profile of steroid hormones in stressed mice. Thirty female mice, six in each group (1. control group, 2. mice that received stress, 3. stress mice received 100 mg/kg turmeric (extract daily) for 4 weeks, 4. stress mice received turmeric (extract daily) for 4 weeks and also received adiponectin antagonist, and 5. stress groups received adiponectin antagonist), were used in the current study. The mice first underwent blood sampling. Then all mice were subjected to stress testing before the intervention except one group, which considered as a control group. The intervention in this study was done as a 100 mg/kg turmeric extract that was gavaged daily for each mouse. After the intervention, all mice were tested for sexual behavior, and then blood samples were taken to check serum levels of adiponectin, estradiol, progesterone and prolactin. So, the results showed before the intervention there were no significant difference among 5 group in levels of adiponectin (p = 0.145), estradiol (p = 0.148), progesterone (p = 0.166) and prolactin (p = 0.206) but after intervention there were significant difference between 5 group in levels of adiponectin, estradiol and progesterone (p < 0.001). Also there was significant difference among 5 groups in sexual behavior (p < 0.001). Therefore, consumption of turmeric, which increases serum adiponectin in the stressed mice, can improve sexual function and estradiol hormones profiling., (Copyright © 2021. Published by Elsevier Inc.)

Objective: The clinical utility and prognostic value of WHO 2017 lineage-based classification of pituitary tumours have not been assessed. This study aimed to (1) determine the clinical utility of transcription factor analysis for classification of pituitary tumours and (2) determine the prognostic value of improved lineage-based classification of pituitary tumours., Methods: This was a retrospective evaluation of patients who underwent surgical resection of pituitary tumours at St Vincent's Public and Private Hospitals, Sydney, Australia between 1990 and 2016. Included patients were at least 18 years of age and had complete histopathological data, forming the 'histological cohort'. Patients with at least 12 months of post-surgical follow-up were included in the subgroup 'clinical cohort'. The diagnostic efficacy of transcription factor immunohistochemistry in conjunction with hormone immunohistochemistry was compared with hormone immunohistochemistry alone. The prognostic value of identifying 'higher-risk' histological subtypes was assessed., Results: There were 171 patient tumour samples analyzed in the histological cohort. Of these, there were 95 patients forming the clinical cohort. Subtype diagnosis was changed in 20/171 (12%) of tumours. Within the clinical cohort, there were 21/95 (22%) patients identified with higher-risk histological subtype tumours. These were associated with tumour invasiveness (P = 0.050), early recurrence (12-24 months, P = 0.013), shorter median time to recurrence (49 (IQR: 22.5-73.0) vs 15 (IQR: 12.0-25.0) months, P = 0.005) and reduced recurrence-free survival (P = 0.031)., Conclusions: Application of transcription factor analysis, in addition to hormone immunohistochemistry, allows for refined pituitary tumour classification and may facilitate an improved approach to prognostication.

Background: Although long-term dopamine agonist (DA) therapy is recommended as a first-line treatment for prolactinoma, some patients may prefer surgical treatment because of the potential adverse effects of long-term medication, or the desire to become pregnant. This study aimed to determine whether surgical treatment of prolactinomas could be an alternative to DA therapy., Methods: In this retrospective study, 96 consecutive patients (74 female, 22 male) underwent primary pituitary surgery without long-term DA treatment for prolactinomas at a single institution from 1990 to 2010. All patients underwent primary surgical treatment in the microscopic transsphenoidal approach (TSA)., Results: The median age and median follow-up period were 31 (16-73) years and 139.1 (12.2-319.6) months, respectively. An initial overall remission was accomplished in 47.9% (46 of 96 patients, 33 macroadenomas, and 13 microadenomas) of patients. DA dose reduction was achieved in all patients after TSA. A better remission rate was independently predicted by lower diagnostic prolactin levels and by a greater extent of surgical resection. Overall remission at the last follow-up was 33.3%, and the overall recurrence rate was 30.4%. The permanent complication rate was 3.1%, and there was no mortality., Conclusion: TSA can be considered a safe and potentially curative treatment for selective microprolactinomas as an alternative to treatment with a long-term DA., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Abstract: Bipolar disorder (BD)-mania is related to the dysfunction of anterior pituitary gland, but the pituitary-thyroid interaction on the acute stage of BD has been controversial. In order to rule out the effects of drugs, we aimed to determine the upstream interaction of first-episode of BD type I in mania state, and tried to find the relationship between thyroid-stimulating-hormone (TSH) and Prolactin (PRL)This study included 70 real-world patients diagnosed with first-episode BD-mania recuited and 70 healthy controls (HC) matched for age and sex from 2016 to 2017 in the same district of Shanghai. We compared the levels of thyroid hormones and prolactin between the two groups, and linear regression and curve estimation were used for the correlation analysis of TSH and PRLThere were differences in triiodothyronine (TT3), total thyroxin (TT4), and free thyroxine (FT4) concentrations between the groups (P's < .05). After being grouped by sex, higher PRL in the male and female BD-mania subgroup were observed compared to each isosexual HC [(P's < .01, Cohen's d = 0.82/1.08, 95%CI (0.33, 1.31)/(0.58, 1.58)]. Higher FT4 in the male BD-mania group was observed compared to the HC males [(P's  < .01, Cohen's d = 0.90, 95%CI (0.41, 1.39)] while the female BD-mania group showed lower TT3 and TT4 compared to the HC females [(P's  < .01, Cohen's d = 0.93/0.88, 95%CI (0.43, 1.42)/(0.39, 1.37)]. In the female BD-mania group, correlation analysis established an inverse relationship between PRL and TSH (r2 = 0.25, F = 11.11, P < .01).The findings demonstrate that sex impacts the concentration of hormones secreted by the anterior pituitary of patients with first-episode BD-mania. The increased PRL may be a putative mechanism that underlies the onset in female patients with a moderate inverse relationship between TSH and PRL. Thyroid hormones and prolactin levels may be developed as potential markers for identifying BD-manic., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Breastfeeding is an important health concern for postpartum women. Objective: This study aimed to investigate the effect of breastfeeding frequency on the level of serum prolactin (PRL), milk intake, and infant weight gain. Materials and Methods: The time and duration of each breastfeeding episode were recorded by participants from day 1 to 28 postpartum. According to their diaries, we divided participants into the low-frequency breastfeeding group (Group I; <10 breastfeeding episodes/day) and high-frequency breastfeeding group (Group II; >/ = 10 breastfeeding episodes/day). A total of 23 mother-infant pairs were enrolled; blood samples were drawn between 1600 and 1800 hours. The PRL levels were examined using the DPC Immulite system. Results: Overall, 71.8% (23) of the enrolled mother-infant pairs completed the follow-up. Infant birth weight was higher in Group II than in Group I (3275.6 ± 93.3 g versus 2918 ± 82.1 g). On day 28 postpartum, infants in Group II ingested significantly more milk per feeding (71.6 ± 4.0 mL versus 54.1 ± 5.2 mL) and gained more weight from birth (142.9% ± 4.5% versus 130.2% ± 2.4%) compared with those in Group I. The mothers of Group II had significantly higher basal serum PRL levels (116.4 ± 11.8 ng/mL versus 72.7 ± 7.77 ng/mL), but a significantly lower increase in PRL postsuckling (168.5% ± 23.1% versus 291.6% ± 37.6% of basal PRL). The frequency of suckling was positively correlated ( r  = 0.5) with the basal PRL level. Moreover, infant weight gain was significantly higher in male (144.7% ± 4.7%) than in female (132.3% ± 2.9%) infants. Conclusions: Increase in frequency of breastfeeding of over 10/day is associated with baseline PRL levels and increased milk production and weight gain. These results provide useful information for breastfeeding women.

Background: Amisulpride is an antipsychotic used in a wide range of doses. One of the major adverse events of amisulpride is hyperprolactinemia, and the drug might also induce body weight gain., Objective: The aims of this work were to characterize the pharmacokinetics of amisulpride in order to suggest optimal dosage regimens to achieve the reference range of trough concentrations at steady-state (C min,ss ) and to describe the relationship between drug pharmacokinetics and prolactin and body weight data., Methods: The influence of clinical and genetic characteristics on amisulpride pharmacokinetics was quantified using a population approach. The final model was used to simulate C min,ss under several dosage regimens, and was combined with a direct E max model to describe the prolactin data. The effect of model-based average amisulpride concentrations over 24 h (C av ) on weight was estimated using a linear model., Results: A one-compartment model with first-order absorption and elimination best fitted the 513 concentrations provided by 242 patients. Amisulpride clearance significantly decreased with age and increased with lean body weight (LBW). C min,ss was higher than the reference range in 65% of the patients aged 60 years receiving 400 mg twice daily, and in 82% of the patients aged > 75 years with a LBW of 30 kg receiving 200 mg twice daily. The pharmacokinetic/pharmacodynamic model included 101 prolactin measurements from 68 patients. The E max parameter was 53% lower in males compared with females. Model-predicted prolactin levels were above the normal values for C min,ss within the reference range. Weight gain did not depend on C av ., Conclusions: Amisulpride treatment might be optimized when considering age and body weight. Hyperprolactinemia and weight gain do not depend on amisulpride concentrations. Modification of the amisulpride dosage regimen is not appropriate to reduce prolactin concentrations and alternative treatment should be considered.

Background/aim: Natural products are popular insights for researchers to investigate promising anti-cancer agents since some of these substances have lesser adverse effects restricting the treatment than traditional chemotherapeutic agents. A well-known monoterpene Carvacrol, widely consumed in Mediterranean cuisine and lower risks of cancer, has efficient anticancer effects. However, the mechanism of action is yet to be discovered., Materials and Methods: The investigation aims to illuminate a new perceptive in the role of this substance on colorectal cancer treatment, by the means of differences in a well-defined range of soluble factors. Carvacrol effect on both HT-29 and HCT-116 cell lines was evaluated on proliferation and the IC50 values were calculated by the RTCA xCELLigence device. Then MAGPIX assay was performed to obtain the changes in soluble factors of the cell lines., Results: The Multiplexing assay suggests some of these factors were altered in favor of surviving and proliferation in aggressive cell line HCT-116 whereas they were altered against these characters in HT-29, were correlated with the increased IC50 concentration of HCT- 116 in carvacrol treatment., Conclusion: The current study indicates that differences in the levels of these soluble factors could modulate the anticancer effect related to carvacrol., Competing Interests: None declared, (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Introduction: Approximately one third of pituitary adenomas are manifested neither by specific symptoms of hormone overproduction nor by elevated blood levels of pituitary hormones. However, these tumours, diagnosed before surgical intervention as clinically non-functioning pituitary adenomas (CNFPAs) express in majority different pituitary hormones, as can be revealed by means of immunohistochemical examination. One of the pituitary hormones which may be expressed in CNFPAs is prolactin (PRL) but the clinical and pathological data on this condition are very scarce., Material and Methods: Sixty two pituitary adenomas, diagnosed before surgery as CNFPAs, were immunoassayed with antibodies against PRL, growth hormone (GH), luteinizing hormone (LH), follicle stimulating hormone (FSH), thyrotropin (TSH), alpha subunit (alpha-SU), corticotropin (ACTH) and dopamine receptor type 2. In a proportion of the patients the presurgical concentrations of insulin-like growth factor 1 (IGF-1) were estimated by means of enzyme-amplified chemiluminescence assay., Results: Twenty-three (37.1%) of the examined CNFPAs presented the positive immunoreaction with anti-PRL antibody. Most cases concerned women. Only in two cases (one woman and one man), PRL was the unique hormone expressed in the tumour. In the remaining adenomas PRL immunopositivity was accompanied by GH expression - 17, LH or free bLH - 13, FSH - 2, free a subunit - 4 or by ACTH - 5 tumours. Seven (30.43%) of them were recurrent in comparison with 12.8% PRL-immunonegative recurrent CNFPAs. Dopamine receptors were positively immunostained in all the investigated PRL-immunopositive and all PRL-immunonegative adenomas., Conclusions: Our data confirm the observations that monohormonal silent prolactinomas are very rare but frequently silent PRL often co-expressed with GH or LH. Although in the whole population of patients with CNFPAs both sexes are equally represented, in the case of silent prolactinomas the female sex is prevalent. The observation of the higher rate of recurrent tumours within PRL-immunopositive adenomas versus PRL-immunonegative CNFPAs has to be confirmed on the larger material.

Breast milk is the optimum for all infants, but hospitalization in the neonatal intensive care unit can cause separation of mothers and infants, which often interferes with milk secretion. Some reports show that domperidone is effective in promoting milk secretion. However, the Food and Drug Administration in the United States cautioned to not use domperidone for increasing milk volume because domperidone carries some risk of cardiac events, including QT prolongation, cardiac arrest, and sudden death. In contrast, it is used in Canada, Australia, and the United Kingdom with safety. The pharmacodynamics and pharmacokinetics of drugs may vary by race or ethnic origin, and it is not known whether domperidone is effective or safe for Japanese. In this study we report the effects of domperidone for Japanese mothers with insufficient lactation. Ten mothers were enrolled in a pilot study. After confirming that there were no abnormal findings on the electrocardiogram, the mothers were administered domperidone. Seven of 10 who took domperidone increased their milking volume. Prolactin was increased in 9 of 10 mothers. Adverse events were observed in two mothers, one headache and one abdominal pain; all symptoms were mild and improved promptly; and there were no adverse cardiac events. These results are consistent with reports from other countries. Domperidone may tentatively be considered effective for increasing milk secretion in Japanese mothers as in other populations. Our preliminary study of 10 cases indicates the need for further studies with larger sample sizes to assess the efficacy and safety of domperidone.

Introduction: Macroprolactinaemia is a well-known analytical problem in diagnostics of hyperprolactinaemia usually detected with polyethylene glycol (PEG) precipitation method. Since there is no harmonization in macroprolactin detection and reporting results, this study proposes and evaluates the usefulness of in-house developed algorithm. The aims were to determine the most suitable way of reporting results after PEG treatment and the possibilities of rationalizing the precipitation procedure., Materials and Methods: This is a retrospective study based on extracted data for 1136 patients. Prolactin concentrations were measured before and after PEG precipitation on Roche cobas e601. Macroprolactinaemia was defined by percentage recovery and post-PEG prolactin concentrations., Results: Prevalence of macroprolactinaemia using recovery criteria of ≤ 40%, ≤ 60%, and post-PEG prolactin concentrations was 3.3%, 8.8% and 7.8%, respectively. Raising the cut-off value from the upper limit of the manufacturer's reference interval to 32.9 µg/L does not drastically change detected macroprolactinaemia with recovery criteria. Post-PEG prolactin concentrations showed more than half of the patients with macroprolactinaemia would be overlooked. Regardless of the criteria, a cut-off of 47.0 µg/L would miss most of the macroprolactinaemic patients. Repeated recovery measurements of follow-up patients showed there is a significant difference with mean absolute bias of 9%., Conclusions: Post-PEG prolactin concentration with corresponding reference interval is the most suitable way of reporting results. All samples with prolactin concentration above the upper limit of the manufacturer's reference interval should be submitted to PEG precipitation. Follow-up period could be prolonged since the difference between the recoveries of repeated measurements is not clinically significant., Competing Interests: Potential conflict of interest: None declared.

Background and objectives : Burnout is a syndrome typically occurring in work environments with continuous and chronic stress. Physicians are at increased risk for burnout, as a result of 24-hour work, delayed work-life balance gratification, and the challenges associated with patient care. The aim of the present study was to evaluate the psychological parameters of burnout symptoms in relation to biomarkers of stress among physicians with different medical specialties. Materials and methods : A total of 303 physicians were contacted as potential participants. A comparison group of 111 individuals working outside medicine was used as a control to verify the results. The physicians were specialists in internal medicine, general surgery, pathology, and primary care. Serum cortisol, salivary cortisol, adrenocorticotropic hormone (ACTH), insulin (IRI), and prolactin levels were analyzed by chemiluminescence enzyme immunoassay (Access 2, Beckman Coulter). Fasting glucose in serum and glycated hemoglobin (HbA1C) in whole blood were measured using the automatic analyzer AU 480 Beckman Coulter system. Symptoms of burnout were measured with the Maslach Burnout Inventory (MBI). Results : The group with burnout presented significantly higher levels of serum and saliva cortisol, ACTH, prolactin, fasting glucose, and HbA1C compared with the control group. The correlation analysis between biomarkers showed a positive correlation with moderate strength between serum and saliva cortisol ( r = 0.516, p = 0.01),as well as serum and saliva cortisol with ACTH ( r = 0.418; r = 0.412, p = 0.01) and HbA1C ( r = 0.382; r = 0.395, p = 0.01). A weak positive correlation was found between serum and saliva cortisol with prolactin ( r = 0.236; r &nbsp;=&nbsp;0.267, p < 0.01) and glucose ( r = 0.271; r = 0.297, p < 0.01). In the multiple logistic regression model, saliva cortisol, HbA1C, and age were significantly associated with burnout (chi-square = 16.848, p &nbsp;<&nbsp;0.032). Conclusion : Our findings demonstrated the interest of exploring biomarkers of stress related to burnout in health professionals., Competing Interests: The authors declare no conflict of interests.

Objectives: This study aimed to evaluate the aetiologies of hyperprolactinaemia in the United Arab Emirates (UAE)., Methods: This retrospective study used laboratory databases to identify all patients who underwent evaluation for prolactin at Tawam Hospital, Al Ain, UAE, between 2009 and 2015. Of those 2,280 patients, all patients with low or normal prolactin (n = 1,315) were excluded. Subsequently, charts of the remaining patients (n = 965) with hyperprolactinaemia were reviewed and those with incomplete work-ups or insufficient documentation of the hyperprolactinaemia's aetiology were excluded (n = 458)., Results: A total of 507 patients were included in the study. The average age at prolactin evaluation was 36 ± 13.2 years and the majority (67.1%) of patients were female. The most common reasons for requesting prolactin were menstrual disorders (29.5%), infertility (18%), evaluation of sellar masses (14.3%), ruling out seizures (13.4 %) and monitoring while on psychiatric medications (8.7%). The most common causes of hyperprolactinaemia were prolactinoma (17%), transient hyperprolactinaemia (14.6%), drug-induced side effects (14.4%), polycystic ovarian syndrome (11.8%) and seizure disorder (7.7%). In females, common aetiologies were prolactinomas, transient and idiopathic hyperprolactinaemia, while sellar masses, seizures, chronic kidney disease and acute illnesses were common aetiologies of hyperprolactinaemia in males. The prolactin level varied between the different aetiologies and a level of >250 ng/mL was suggestive of macro-prolactinoma., Conclusion: A significant proportion of patients with hyperprolactinaemia have transient hyperprolactinaemia. Before further investigations are carried out, prolactin level assessment should be repeated, especially in patients with mild hyperprolactinaemia., Competing Interests: CONFLICT OF INTEREST The authors declare no conflicts of interest.

Prevalence and incidence of prolactinomas are approximately 50 per 100,000 and 3-5 new cases/100,000/year. The pathophysiological mechanism of hyperprolactinemia-induced gonadotropic failure involves kisspeptin neurons. Prolactinomas in males are larger, more invasive and less sensitive to dopamine agonists (DAs). Macroprolactin, responsible for pseudohyperprolactinemia is a frequent pitfall of prolactin assay. DAs still represent the primary therapy for most prolactinomas, but neurosurgery has regained interest, due to progress in surgical techniques and a high success rate in microprolactinoma, as well as to some underestimated side effects of long-term DA treatment, such as impulse control disorders or impaired quality of life. Recent data show that the suspected effects of DAs on cardiac valves in patients with prolactinomas are reassuring. Finally, temozolomide has emerged as a valuable treatment for rare cases of aggressive and malignant prolactinomas that do not respond to all other conventional treatments., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

BACKGROUND The aim of this study was to evaluate the risk factors of gonadal dysfunction among Chinese women of reproductive age with pituitary adenomas (PAs) after trans-sphenoidal surgery. MATERIAL AND METHODS We retrospectively evaluated 317 women (16-44 years old) who underwent gonadal function and hormone testing before and after trans-sphenoidal surgery for PAs during 2003-2012. Gonadal function was assessed on the basis of menstrual status. RESULTS Three women were excluded because of pre-existing gynecological diseases. Before trans-sphenoidal surgery, 34 (10.7%) women were eugonadal and 283 (89.3%) women had gonadal dysfunction. After trans-sphenoidal surgery, 130/189 (68.7%) women with follow-up menstruation data were eugonadal, and 59/189 (31.2%) women exhibited gonadal dysfunction. In addition, 67.4% women of reproductive age with PAs and gonadal dysfunction were restored by trans-sphenoidal surgery (P<0.01). Postoperative gonadal dysfunction was independently associated with high prolactin level at day 1 after trans-sphenoidal surgery (odds ratio (OR)=1.024; 95% confidence interval (CI)=1.005-1.043; P=0.012) and tumor invasion (OR=5.752; 95%CI=1.618-20.447; P<0.01). Based on the receiver operating characteristic (ROC) curve, prediction of gonadal dysfunction in women of reproductive age after trans-sphenoidal surgery for PAs using prolactin >46.82 µg/L on postoperative day 1 had sensitivity of 88%, specificity of 95%, positive predictive value of 98%, and negative predictive value of 76%, and an area under the ROC curve of 0.701. CONCLUSIONS Gonadal dysfunction is very common in Chinese women of reproductive age with PAs and can be effectively restored by trans-sphenoidal surgery. Prolactin >46.82 µg/L at 1 day after trans-sphenoidal surgery and tumor invasion can predict postoperative gonadal dysfunction in these patients.

BACKGROUND This study aimed to investigate the relationship between serum profiles of prolactin and thyroid stimulating hormone (TSH) and sexual dysfunction in patients with schizophrenia treated with conventional antipsychotic medication. MATERIAL AND METHODS A hospital-based cross-sectional study included 118 patients, age range 18-57 years (55 men, 63 women), with a confirmed diagnosis of schizophrenia. All patients were stable after antipsychotic treatment. Serum levels of hormones, including prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone, testosterone, thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3) and free thyroxine (FT4), were detected in venous blood. The Positive and Negative Syndrome Scale (PANSS) score was used to measure symptom severity of patients with schizophrenia. The Mandarin Chinese version of the Arizona Sexual Experience Scale (ASEX), a 5-item scale, was used to measure sexual function. RESULTS There were 66 patients (55.9%) who had hyperprolactinemia, the prevalence of hyperprolactinemia was markedly higher in the sexual dysfunction group than the non-sexual dysfunction group (91.8% vs. 17.5%) (P<0.001). Mean prolactin levels were significantly increased in patients with sexual dysfunction compared with the patients without sexual dysfunction (P<0.001), with a higher incidence in female patients. Subclinical hypothyroidism and hyperprolactinemia were found to be independently associated with sexual dysfunction, and an increased PANSS negative score was an independent risk factor for the development of sexual dysfunction. CONCLUSIONS The incidence of sexual dysfunction was significantly increased in patients with schizophrenia. Hyperprolactinemia and subclinical hypothyroidism were associated with sexual dysfunction, especially in female patients.

BACKGROUND The aim was to develop and assess a general pituitary hormone score to evaluate the function of the anterior pituitary (adenohypophysis) in patients following resection of pituitary adenomas. MATERIAL AND METHODS Sixty-six patients with pituitary null cell macroadenoma (1-3 cm diameter) (N=38) and pituitary null cell giant adenoma (≥3 cm diameter) (N=28) had preoperative and postoperative data including magnetic resonance imaging (MRI) and measurement of six pituitary hormones levels, adrenocorticotropic hormone (ACTH), growth hormone (GH), thyroid-stimulating hormone (TSH), prolactin (PRL), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The postoperative general pituitary hormone score, for 57 patients who underwent subtotal resection (>60%) and nine patients who underwent partial resection (≤60%), was 1-5 for each hormone level (score range, 6-30). RESULTS ACTH, GH, TSH, PRL, FSH, and LH levels in 38 patients with pituitary null cell macroadenoma were not statistically different from the 28 patients with pituitary null cell giant adenoma; the general pituitary hormone score in the former group was significantly increased compared with the latter group (P<0.05). ACTH, GH, TSH, PRL, FSH, and LH levels in the 57 patients with subtotal tumor resection were not significantly different from the nine patients with partial tumor resection; the general pituitary hormone score in the former group was significantly reduced compared with the latter group (P<0.05). CONCLUSIONS A general pituitary hormone score was developed that might be relevant to the evaluation of pituitary function following surgical resection of pituitary null cell macroadenoma and giant adenoma.

The fabrication of a novel electrochemical immunosensor for rapid and precise determination of prolactin was carried out using carbon paste electrode (CPE) consist of ionic liquid (IL) and graphite. Gold nanoparticles were employed as a modifier on the surface of CPE to immobilize the prolactin antibody (anti-PRL). The immunoassay was set up by sandwiching the antigen between prolactin antibody and the polyclonal anti-human-prolactin antibody labeled with horseradish peroxidase (HRP-labeled anti-PRL) as secondary antibody, on the surface of modified CPE. The reaction between O-aminophenol (OAP) and H 2 O 2 which is catalyzed by labeled HRP on the sandwich immunosensor generate a signal in differential pulse voltammetry (DPV) that is used to determine the concentration of prolactin. This immunosensor provides the measurement of prolactin concentration in a linear range of 25.0-2000.0 mIU L -1 with a detection limit 12.5 mIU L -1 . Moreover, it is applicable in the clinical assay of prolactin due to its high sensitivity and acceptable stability., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To characterize US clinical laboratory reference range reporting and testing methods of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and prolactin., Methods: One hundred and seventeen US laboratories were surveyed. Outcomes measured were variation in lower and upper limits of normal male reference ranges for serum FSH, LH, estradiol, and prolactin, method of analysis and source of reference range RESULTS: The upper limit of normal reference ranges for FSH, LH, estradiol, and prolactin varied substantially across laboratories compared to the lower limits. The range of upper limits of FSH, LH, estradiol, and prolactin respectively are 7.9-20.0, 4.9-86.5, 37.7-77.0, and 7.4-25.0. Ninety-four percent of laboratories performed measurements on in-house high throughput analyzer utilizing immunoassays. Seventy percent of reported reference ranges for each hormone were based on validation studies of the analyzer's package insert values. Ten percent of laboratories derived their own reference ranges. Both the validation studies and derivations were based on a limited number of patient samples, ranging from 20 to 200., Conclusion: Current reference ranges are based on small population studies of men with unknown medical histories, sexual or reproductive function. Influence of race and age has not been evaluated and could potentially be important in normal variation. The absence of standard information has yielded a spectrum of upper and lower normal values, which could delay an appropriate male infertility evaluation. Our findings highlight the need for a large population study of males with known normal sexual and reproductive function to formulate more accurate clinical reference ranges., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Toxocariasis is a zoonotic disease produced by ingestion of larval Toxocara spp. eggs. Prolactin (PRL) has been considered to have an important role in Toxocara canis infection. Recent evidence has found that PRL directly can increase parasite growth and differentiation of T. canis The present study, evaluated the effect of high PRL levels on the immune system's response and parasites clearance in chronic infection. Our results showed that hyperprolactinemia did not affect the number of larvae recovered from several tissues in rats. Parasite-specific antibody production, showed no difference between the groups. Lung tissue presented eosinophilic granulomas typical of a chronic infection in all the experimental groups. Flow cytometry analysis was made in order to determine changes in the percentage of innate and adaptive immune cell subpopulations in the spleen, peripheric (PLN) and mesenteric (MLN) lymphatic nodes. The results showed a differential effect of PRL and infection on different immune compartments in the percent of total T cells, T helper cells, T cytotoxic cells, B cells, NK cells, and Tγδ cells. To our knowledge, for the first time it is demonstrated that PRL can have an immunomodulatory role during T. canis chronic infection in the murine host., (© 2018 The Author(s).)

Endometriosis, characterized by the presence of endometrial tissue at ectopic sites, is a leading cause of pelvic pain and subfertility in women. The stromal compartment of the endometrium is considered to play a pivotal role in the establishment and persistence of endometriotic lesions, thus impaired decidualization of these cells may result in enhanced invasion capacity at ectopic sites. Consequently, stimulation of decidualization may alleviate this disease. To analyze the effect of systemically applied compounds on decidualization of ectopic endometrial tissue, endometriosis was induced by suturing human eutopic endometrium to the peritoneum of 22 NOD/SCID mice. Each mouse received four tissue fragments from the same patient. Mice were randomly allocated either to one control and three experimental groups ( n = 4/group) which were treated with progesterone alone or in combination with forskolin or human chorionic gonadotropin for seven days or to one control and one experimental group ( n = 3/group) which was treated with progesterone and human chorionic gonadotropin for 10 days followed by 7 days without treatment. At the end of the experiments, lesions were measured and analyzed for markers of decidualization (FOXO-1, prolactin) and proliferation (Ki-67). Decidualization was induced in the ectopic lesions by systemic treatment in vivo. This induction was significantly stronger after treatment with progesterone in combination with human chorionic gonadotropin than with forskolin or with progesterone alone. Only the combination with human chorionic gonadotropin led to induction of FOXO1 protein expression and a significant physiologic transformation of the ectopic endometrial stromal cells after seven days of treatment. After termination of human chorionic gonadotropin treatment, the decidualization process continued, leading to a significant inhibition of proliferation. Thus, decidualization of human ectopic endometrial tissue can be induced in a humanized endometriosis mouse model in vivo. This model may help to decipher the signal pathways involved in this decidualization process and to develop novel therapeutical approaches to alleviate this painful disease. Impact statement Impaired decidualization of endometrial stromal cells may contribute to the development of endometriosis, and an increased decidualization reaction may prevent or alleviate this prevalent gynecological disease. Human chorionic gonadotropin (hCG) has been shown to promote decidualization in eutopic endometrium. Up to now in vitro studies mainly used cAMP for successful induction of decidualization of isolated endometrial stromal cells. Here, for the first time, decidualization of ectopic endometrial lesions is induced in an experimental endometriosis mouse model, comparing the effectiveness of hCG with that of the direct adenylyl cyclase activator Forskolin. In this 3D-organ structure in vivo, hCG proved to be more effective in the induction of decidualization than forskolin. Particularly in case of progesterone resistance, alternative pathways inducing decidualization could alleviate endometriosis, and the sophisticated hCG action could constitute a therapeutical tool to induce terminal differentiation in ectopic endometrial lesions.

Background: Online haemodiafiltration (OL-HDF) is currently the most effective dialysis technique that also improves survival. To date, high permeability membranes with low albumin loss, such as polysulfone, polyamide and polyacrylonitrile membranes have been the most widely used. However, the initially restricted use of cellulose triacetate (CTA) membranes in OL-HDF has expanded. The aim of the study was to ascertain whether the latest generation asymmetric CTA membranes are more effective in obtaining high convective transport., Patients and Methods: A total of 16 patients (10 males and 6 females) undergoing OL-HDF were studied. Each patient underwent 4 different sessions, with haemodialysis or OL-HDF, and/or with CTA or asymmetric CTA 1.9 m 2 membranes. Each session was assigned in a randomised order. Serum levels of urea, creatinine, β 2 -microglobulin, myoglobin, prolactin, α 1 -microglobulin, α 1 -acid glycoprotein and albumin where measured at the beginning and end of each session to obtain the reduction rate. The loss of solutes and albumin was quantified from the dialysate., Results: A significantly greater replacement volume in OL-HDF (32.1±3.1 vs. 19.7±4.5 l, P<.001) was obtained by using asymmetrical CTA membranes compared to conventional CTA membranes. Regarding uraemic toxin removal, both membranes obtained similar results for small molecules, whereas asymmetric CTA membranes achieved better results for large molecules, increasing the reduction ratio by 29% for β 2 -microglobulin, 27.7% for myoglobin, 19.5% for prolactin, 49% for α 1 -microglobulin and double for α 1 -acid glycoprotein (P<0.001 in all situations). The loss of albumin was less than 2g for all treatment sessions., Conclusion: Latest-generation asymmetric CTA have proven to be effective in attaining OL-HDF objectives without increased albumin loss., (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

The clinical influence of macroprolactin (MPRL) is not clearly understood and the rate of patients potentially affected by MPRL is unknown. We investigated the influence of MPRL on the onset of galactorrhea and estimated the rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea. Data of patients with obstetric or gynecological symptoms who had undergone PRL fractionation testing were retrospectively analyzed. To evaluate factors influencing galactorrhea, a multivariate logistic regression analysis was performed and the adjusted odds ratios of MPRL for galactorrhea were calculated. Cutoff values for the total PRL level and the proportion of MPRL fractions for galactorrhea were determined by ROC analysis using a multivariate logistic model. The prevalence of patients with a proportion of MPRL fraction greater than or equal to the cutoff value for galactorrhea was estimated. The median proportion of MPRL fraction was 30.1% and increased as PRL level increased. Total PRL and MPRL had a significant influence on the onset of galactorrhea and the adjusted odds ratio was 1.09 in total PRL and 0.94 in MPRL. The rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea was estimated to be 33.5% of the study population, and thus found to be twelve times or more the number of macroprolactinemia patients. Future prospects for hyperprolactinemia may require diagnostic criteria using free prolactin levels and so MPRL fraction measurement is important for the diagnosis and treatment of patients with obstetric and gynecological symptoms.

Background: Empty sella is the neuroradiological or pathological finding of an apparently empty sella turcica containing no pituitary tissue. The prevalence of primary empty sella, i.e., empty sella without any discernible cause, is not precisely known; estimates range from 2% to 20%. Technical advances in neuroradiology have made empty sella an increasingly common incidental finding. It remains unclear whether, and to what extent, asymptomatic adult patients with an incidentally discovered empty sella should undergo diagnostic testing for hormonal disturbances., Methods: To answer this question, the authors carried out a systematic search in the PubMed and Web of Science databases for publications that appeared in the period 1995-2016 and that contained the search term "empty sella" (registration: PROSPERO 2015: CRD42015024550)., Results: The search yielded 1282 hits. After the exclusion of duplicates, pediatric reports, case reports, and veterinary studies, 120 publications on primary empty sella syndrome (PES) were identified. 4 of these dealt with the prevalence of pituitary insufficiency in patients with PES as an incidental finding. Among patients with PES, the relative frequency of pituitary insufficiency in the pooled analysis was 52% (95% confidence interval [38; 65])., Conclusion: The data on PES as an incidental finding are too sparse to enable any evidence-based recommendation on the potential indications for hormone testing or its nature and extent. We advise basic neuroendocrinological testing (fasting cortisol, free thyroxine [fT4], estradiol or testosterone, insulin-like growth factor 1 [IGF-1], and prolactin). There is an unexplained discrepancy between the reported high prevalence of pituitary insufficiency among persons with PES and its low prevalence in epidemiologic studies. We suspect that the former may be high because of selection bias in the publications that we reviewed, or else the latter may be erroneously low.

Introduction: Online haemodiafiltration (OL-HDF) has been associated with increased survival. To date, the influence of the inner diameter of the hollow fibres of the dialyser on convective volume has not been well established. The objective of the study was to evaluate the effect of increasing the inner diameter of the dialyser on the convective volume and removal capacity., Material and Methods: We included 16 patients in posdilutional OL-HDF with autosubstitution. Each patient was analysed in 4 sessions in which the inner diameter varied; 185μm (FX60 Cordiax and FX80 Cordiax) versus 210μm (FX600 Cordiax and FX800 Cordiax). Different solutes were measured at the beginning and end of each dialysis session., Results: No differences in the convective volume were found with an increased inner diameter: 32.3±3.1 vs. 31.8±3.6 l/session (FX60 vs. FX600) and 33.7±4.3 vs. 33.5±3.8 l/session (FX80 vs. FX800). The reduction percentages also did not differ: urea 83.7±4.5 vs. 84.1±3.4 for FX60 and FX600, and 82.7±4.1 vs. 83.6±3.8 for FX80 vs. FX800; creatinine similar 78.2±5.6 vs. 77.8±4.6 y 77.1±5.4 vs. 78.1±4.9; β 2 -microglobulin 82.2±4.3 vs. 82.9±4.2, and 82.9±4.7 vs. 84.0±3.8; myoglobin 71.0±10 vs. 70.2±9 and 72.8±11 vs. 75.0±10; prolactin 70.4±9 vs. 68.1±9, and 72.2±10 vs. 73.4±8.2; and α 1 -microglobulin 22.9±10 vs. 21.6±10, and 26.5±12 vs. 28.8±11, respectively., Conclusion: The increase in the inner diameter of the hollow fibres did not result in improved convective volume and removal capacity., (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Proteolytic cleavage through proteases affects peptide hormone levels, which is of particular significance when the time interval between sampling and analysis is prolonged. We evaluated the stability of parathyroid hormone, insulin, and prolactin molecules (i) with different protease inhibitors such as K 2 EDTA, aprotinin, and protease inhibitor cocktail (PIC), (ii) with different lag times (6-72 hours), and (iii) under different storage temperatures (4°C vs room temperature [RT]) until analysis., Materials and Methods: Blood samples were collected into 2 sets of 5 Vacutainer ® tubes (Becton Dickinson) from 10 healthy adults. Tubes 1 and 2 were plain gel separator tubes. Tubes 3, 4, and 5 contained PIC (1%), aprotinin (500 KIU/mL), and K 2 EDTA, respectively. After centrifugation at 1300 g for 10 minutes, PIC added to tube 2 of each set. Samples were analyzed and then one set was stored at 4°C, whereas the other at RT until analysis at 6, 24, 48, and 72 hours. Hormone levels were determined with electrochemiluminescence immunoassay (ModularE170; Roche Diagnostics). The results were compared with desirable bias limits (DBL) from Westgard QC database., Results: Insulin at RT decreases exceeding the DBL starting from 24 hours and K 2 EDTA preserved insulin. PTH exceeded the DBL at RT for 48 hours or longer and PIC addition after centrifugation inhibited its degradation. Prolactin remained stable in all tested conditions. All parameters in the plain gel separator tubes remained within DBL when stored at 4°C until 72 hours., Conclusions: Different proteases may degrade peptide hormones and measures should be taken to counteract these effects especially if there is a delay before analysis., (© 2017 Wiley Periodicals, Inc.)

Background: Acromegaly is caused by elevated secretion of human growth hormone, which is frequently because of intracranial tumors. This diagnosis is fairly uncommon with an incidence of 3 to 4 cases per million patients per year. We are presenting a case of acromegaly diagnosed in an active duty Chief Petty Officer., Materials and Methods: A 38-year-old male Chief Petty Officer with no previous mental health diagnosis experienced post-traumatic stress disorder (PTSD)-like symptoms in early 2012 after deploying to Iraq and Afghanistan from 2010 to 2011. Initially he self-managed his symptoms, but in July 2012 he required a reduction mammoplasty because of gynecomastia. The metabolic workup revealed elevated prolactin, but this was not further investigated. His recovery from anesthesia was complicated by intensified PTSD-like symptoms, which continued to worsen after the surgery. On self-referral to mental health, he was diagnosed with PTSD and managed for 6 months with cognitive behavioral therapy. Because of persistent and worsening symptoms, his therapy was augmented to include continued cognitive behavioral therapy, alpha-blockers, antidepressants, antihistamines, and sleep aids. Because of night sweats, the selective serotonin reuptake inhibitors doses were modified. Night sweats persisted, and the patient was re-evaluated for other potential etiologies. On evaluation, the patient endorsed a history of obstructive sleep apnea, cervicalgia, visual changes, depressed mood, as well as multiple physical symptoms including coarsened facial features, large hands/feet, and increased interdental distance. On laboratory analysis, insulin-like growth factor 1 was noted to be 3 times the upper limit of normal, and a prolactin level was five times the upper limit of normal. A brain magnetic resonance imaging revealed a cystic pituitary lesion with suprasellar extension, compression of the infundibulum without invasion of the cavernous sinus, or displacement of the optic chiasm. Based on clinical history, physical examination, laboratory data, and the pituitary lesion, this patient was diagnosed with acromegaly. He was referred to neurosurgery for further evaluation and management., Results and Conclusion: This case shows that side effects of medications can easily mimic some medical conditions. The possibility of unrecognized disease should not be overlooked simply because a patient's symptoms that develop after starting a medication correspond well the side effect profile of the prescribed medications. This is especially true if side effects do not stop with alteration of medication dose, cessation of the medication, or changing to another medication. Pituitary adenomas are rare in patients treated for PTSD. However, attribution of PTSD patient's symptoms to the side effects of selective serotonin reuptake inhibitors therapy without considering a broader differential may lead to a missed diagnosis of an endocrine disease. In this case, the presence of an undiagnosed pituitary lesion resulted in ineffective medical management of PTSD in the patient. Mental health providers should remain allied with their primary care counterparts and consider directing patients to primary care for periodic physical re-evaluation to provide the most effective approach to symptom evaluation and management., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)

It is now widely accepted in human medicine that prolactin (PRL) and growth hormone (GH) function in the mammary gland in an autocrine and paracrine manner in tumour formation. The aim of this study was to compare PRL and GH immunoactivity in canine mammary tumours submitted for histopathologic evaluation. Formalin-fixed specimens from spontaneously occurring mammary adenomas and adenocarcinomas from 24 female client-owned dogs were used. Information pertaining to the reproductive status of the patient at the time of mammary tumour diagnosis was obtained from each of the submitting veterinarians. Tissues were paraffin-embedded and sectioned (5 μm) onto charged slides. All slides were deparaffinized and rehydrated. Endogenous peroxidase activity was inactivated with 3% H 2 O 2, and non-specific binding was blocked. Polyclonal rabbit antihuman PRL (DAKO A0569) and GH antibody (DAKO A0570) were applied at a 1:250 and 1:200 dilutions, respectively. A universal rabbit negative control (DAKO N1699) was used. Slides were then reacted with anti-rabbit horseradish peroxidase followed by Nova Red Peroxidase substrate. Slides were counter-stained with haematoxylin, dehydrated and mounted. Tumour type and reproductive status at time of tumour diagnosis were compared individually between tumours that were negative or positive for PRL and GH using a two-tailed analysis of variance. Significance was defined as p < .05. There was no significant relationship between tumour type and PRL and GH presence. In addition, reproductive status at the time of tumour removal was found to be not significant. These results vary from previous reports in canine mammary tumours and warrant further investigation., (© 2016 Blackwell Verlag GmbH.)

In this study, the concentration of prolactin, FT4, and semen quality were investigated in 5 clinically healthy fertile mixed-breed dogs (1-3 years old) treated with cabergoline (5μg/kg) during 9 weeks. Semen analysis was performed for volume, live or dead, concentration, and motility factors every week. The results indicated that cabergoline administration caused a minor but significant reduction of the mean prolactin concentration (P < .05) and did not affect the secretion of FT4 (P > .05). Further, there was not a significant effect of cabergoline on semen quality, statistically. We could not find any relationship between prolactin and FT4 concentration and changes in semen characteristics., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The objectives of this study were to determine the role of glucocorticoids in the regulation of prolactin (PRL) release induced by mammary gland stimulation and to investigate whether the milk depression induced by glucocorticoids in dairy cows is due to a decrease in PRL release. In experiment 1, 8 dairy cows were used in a 4 × 4 Latin square design. Four hours after the morning milking, the cows received 1 of the following treatments: (1) a 5-min manual stimulation of the mammary gland; (2) an i.v. injection of 1 mg of dexamethasone; (3) 2 infusions of 2.5 g of metyrapone (an inhibitor of cortisol biosynthesis) in the omasum 4 and 2 h before a 5-min stimulation of the mammary gland; or (4) no treatment. Sixty minutes later, the mammary gland of each cow was stimulated for 5 min. Blood samples were collected from 20 min before to 120 min after the start of the treatment. When the mammary gland was stimulated twice in 60 min, less PRL and cortisol were released during the second stimulation. Metyrapone did not affect PRL or cortisol release. Dexamethasone decreased serum cortisol concentration but did not affect PRL concentration. In experiment 2, 16 cows were used in a crossover experimental design consisting of 2 experimental weeks separated by 1 resting week. During the first week, cows were treated as follows: (1) 4 cows were injected with 0.5 g of domperidone (a PRL secretagogue) in canola oil on d 1 and 2 and 20 mg of dexamethasone on d 1; (2) 4 cows were injected with 0.5 g of domperidone on d 1 and 2; (3) 4 cows were injected with canola oil on d 1 and 2 and with 20 mg of dexamethasone on d 1; and (4) 4 cows were injected with canola oil on d 1 and 2. During the second experimental week, the same 4 treatments were repeated, except the cows that did not receive dexamethasone in the first week received it on d 1 of the second week, and cows that did receive it in the first week did not receive it in the second week. On d 1 and 2 of each week, blood samples were collected during morning milking for PRL determination. Dexamethasone reduced milk production and decreased both basal and milking-induced PRL release. It also increased milk fat and protein percentages and decreased milk lactose content. Domperidone increased basal PRL levels in serum and milk but did not affect milk yield. Although we cannot rule out the possibility that inhibition of PRL secretion or reduction of mammary gland PRL responsiveness play a role in the inhibition of milk production by glucocorticoids, the fact that enhancement of PRL secretion by domperidone could not prevent the depression of milk yield suggests that other mechanisms are involved., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background/aims: Aberrant expression of miRNA has been found in many tumor tissues to regulate the tumorigenesis by binding to the 3`- untranslated region (3`-UTR) of the target genes. The aim of this study is to investigate the role of miR-148b, miR-152/ALCAM axis in human pituitary adenomas (PAs)., Methods: First, we detected the expression level of miR-148b-3p and miR-152 in human PAs samples by using qRT-PCR. Then we studied the role of miR-148b-3p, miR-152 on human PAs cell proliferation, invasion and apoptosis by using MTS assay, Transwell invasion assay and Annexin V/PI Staining Test. To study the relationship between miR-148b-3p, miR-152 and activated leukocyte antigen molecule (ALCAM), we overexpressed miR-148-3p or miR-152 by transfecting specific mimics. Lucifearase reporter assay was then performed to confirm the target. Next, we studied the biological functions of ALCAM in human PAs cells. Finally, the role of miR-148b-3p, miR-152/ALCAM axis in PAs cells was studied., Results: The expression level of miR-148-3p and miR-152 in invasive PAs samples was lower than those in noninvasive samples. Overexpression of miR-148b-3p, miR-152 could repress proliferation and invasion, and promote apoptosis. Moreover, miR-148b-3p and miR-152 could repress activated leukocyte antigen molecule (ALCAM) expression. Knockdown of ALCAM could repress proliferation and invasion and promote apoptosis. By contrary, overexpression of ALCAM promoted proliferation and invasion. Further, the rescue experiments indicated that overexpression of ALCAM significantly restored the proliferation, apoptosis, and invasion influenced by miR-148b-3p and miR-152., Conclusions: Our study suggests that miR-148b-3p, miR-152 may serve as suppressors in PAs through downregulating ALCAM expression. miR-148b, miR-152/ ALCAM axis may be a new therapeutic target in the future., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Adenomyosis is uterine dysfunction defined as the presence of endometrial glands within the myometrium. It is suggested that adenomyosis is estrogen-dependent pathology, and prolactin (PRL) also affects its development. In the uterus of ruminants, PRL stimulates gland proliferation and function. We hypothesized that in the bovine uterus, the expression of PRL and its receptors (PRLRs) during adenomyosis is disturbed and modulated by estradiol (E 2 ). Uterine tissues were collected postmortem from cows; epithelial, stromal, and myometrial cells were isolated; and cultured and treated with E 2 . Material was divided into 2 groups: control (nonadenomyotic) and uteri with adenomyosis. In adenomyotic uterine tissue, PRL and its long-form receptor protein were increased, as determined by Western blotting. Immunohistostaining showed that during adenomyosis, PRL and its receptors are highly expressed in adenomyotic lesions. In cultured myometrial cells, protein expression of PRL and its receptors was increased during adenomyosis. Estradiol decreased PRLRs protein expression in nonadenomyotic stromal cells and in adenomyotic myometrial cells, and increased PRL secretion by adenomyotic myometrial cells. Moreover, PRL secretion was increased in untreated epithelial and stromal cells during adenomyosis. On the other hand, in stromal cells, PRLRs messenger RNA and protein expression was decreased, as determined by real-time PCR and Western blotting, respectively. Obtained results show that significant changes in PRL and PRLRs expression are observed in uterine tissue and cells during adenomyosis, which were also affected by E 2 . These data suggest involvement of PRL in adenomyosis development and the link between PRL and E 2 actions during the dysfunction in cows., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To investigate the therapeutic effects and duration of bromocriptine treatment during pregnancy in patients with pituitary prolactinoma., Materials and Methods: A retrospective analysis of the clinical data of 230 female pituitary prolactinoma patients at the Beijing Union Medical College Hospital neurosurgery clinic from January 2001 to May 2014 was conducted. When confirmed pregnant, patients in the control group immediately stopped taking bromocriptine, but patients in the treatment group continued to take the same dose of bromocriptine., Results: The embryos stop rate in the control group was 16.7%, significantly higher than the rate in the natural population (p < 0.05), while the rate in the treatment group (0.9%) not statistically different from that of the natural population (p > 0.05). There was no significant difference in the embryonic malformation rate between the two study groups compared to the normal pregnancy group (p > 0.05)., Conclusion: Pregnant pituitary prolactinoma patients should not stop bromocriptine treatment, but should instead continue with the same dose for four months. For patients with macroadenoma, bromocriptine should be taken during the entire pregnancy. Blood prolactin, progesterone, human chorionic gonadotropin (hCG), and visual dysfunction should be monitored every two weeks during treatment. Patients should be treated with progesterone and hCG if the blood levels become too low. If regular monitoring shows that prolactin has increased too fast and/or visual dysfunction worsened, the dose of bromocriptine should be in- creased. The authors have found that bromocriptine treatment during pregnancy significantly reduces the embryo stop rate without in- creasing the embryo deformity rate; therefore, bromocriptine treatment is safe and necessary during pregnancy of pituitary prolactinoma patients.

In recent years, quantum dots (QDs) have been widely used in upcoming nanotechnology-based solar cells, light-emitting diodes and even bioimaging, due to their tunable optical properties and excellent quantum yields. But, such nanostructures are currently constituted by heavy elements which can threat the human health and living environment. Hence, in this work, the in vivo effects of CdTe nanocrystals (NCs) (as one of the promising QDs) on spermatozoa of male mice and subsequently on fertility of female mice were investigated, for the first time. To do this, CdTe NCs were synthesized through an environment-friendly (aqueous-based solution) method. The sperm cells presented a high potential for uptake of the heavy QDs. Meantime, the NCs exhibited concentration-dependent adverse effects on morphology, viability, kinetic characteristics and DNA of the spermatozoa. At low concentration of 0.1μg/mL, the NCs showed a moderate toxicity (~25% reduction in viability and motility of the spermatozoa), while remarkable toxicities were observed at higher concentrations of 1.0-100μg/mL (~67% reduction in viability and motility for 100μg/mL). Furthermore, significant in vitro DNA fragmentation of the spermatozoa was observed at CdTe concentrations ≥10μg/mL. In vivo toxicity of the NCs was found lower than the in vitro toxicity. Nevertheless, the in vivo destructive effects of the NCs still caused ~34% reduction in viability as well as motility and ~5% damages in DNA of male mice spermatozoa. These resulted in ~26% decrease in fertility and gestation of female mice, along with an overall hormone secretion during the pregnancy, and ~39% reduction in viability of pups/pregnant females., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Macroprolactinaemia is a major cause of hyperprolactinaemia. The detectability of macroprolactin varies widely among different immunoassay systems, but the causes are not fully known. This study aimed to identify the factors influencing the detectability of macroprolactin by immunoassay systems., Methods: The study included 1544 patients who visited an obstetric and gynaecological hospital. Macroprolactinaemia was screened using the polyethylene glycol (PEG) method and confirmed using gel filtration chromatography and the protein G method. The prolactin (PRL) values determined by enzyme immunoassay (EIA) were compared with those of a chemiluminescence immunoassay system (Centaur) that is known to cross-react the least with macroprolactin., Results: Macroprolactinaemia was found in 62 of 1544 patients (4.02%) who visited an obstetric and gynaecological hospital. The ratio of EIA-determined total PRL to free PRL in the supernatant after PEG precipitation was significantly elevated in all 62 serum samples with macroprolactin compared to those in 1482 serum samples without macroprolactin. In contrast, the ratio of Centaur-determined total PRL to free PRL was significantly elevated in 32 serum samples (group 1) and was within the normal range in 30 (group 2) of 62 serum samples with macroprolactin. The prevalence of non-IgG-type macroprolactin was significantly higher in group 1 than in group 2. Centaur diagnosed hyperprolactinaemia less frequently than EIA (n=2 vs. 16) in 62 patients with macroprolactinaemia. Those two hyperprolactinaemic patients diagnosed by Centaur had non-IgG-type macroprolactin., Conclusions: Macroprolactinaemia was present in 4% of patients visiting an obstetric and gynaecological hospital. The nature of macroprolactin (IgG-type or non-IgG-type) may partly explain why macroprolactin detectability varies among different immunoassay systems.

Objectives: Breastfeeding has positive effects for both, the mother and the infant. The purpose of the study was to ex-amine how cesarean delivery and vaginal delivery influenced subsequent breastfeeding. The study was conducted at the Kırıkkale University Medical School., Material and Methods: Breastfeeding outcomes after an elective cesarean delivery and after a planned vaginal delivery were compared. The study included 169 consenting mothers who gave birth to healthy infants (86 cesarean deliveries and 83 vaginal deliveries) between March and September 2001. All cesarean deliveries were performed under regional anesthesia., Results: Elective cesarean delivery was performed at a significantly earlier gestational age as compared to vaginal delivery (p = 0.001). Maternal age in the planned vaginal delivery group was significantly lower (p = 0.003). As for the change in prolactin levels, the results were similar but not statistically significant (p = 0.21). The frequency of breastfeeding per day did not differ significantly between the groups (p = 0.20). However, women after cesarean delivery tended to breastfeed more often than after vaginal delivery (p = 0.003). Mean number of points recorded at the first breastfeeding session, according to the LATCH charting system, was lower in the group after cesarean delivery as compared to vaginal labor. The difference between the average point scores of vaginal delivery and cesarean delivery mothers was found to be meaningful in favor of the women after vaginal delivery (p = 0.05)., Conclusions: Elective cesarean section has negative effects on breastfeeding. Our results indicate that cesarean section constitutes a risk factor for delayed lactogenesis.

Objective: To review the current literature regarding the prevalence of macroprolactin (macroPRL) in hyperprolactinemic patients and determine recommendations for testing., Methods: An electronic United States National Library of Medicine PubMed search (through October, 2014) was conducted for search term "macroprolactin." Only English-language articles were considered., Results: MacroPRL is an under-recognized cause of elevated prolactin (PRL) and is present in approximately 4% to 40% of hyperprolactinemic patients depending on the referral population. Clinical findings which could be due to hyperprolactinemia are the impetus for testing for PRL. Because of this there is significant overlap in the clinical presentation of patients with true hyperprolactinemia and those with macroPRL, differentiation cannot always be made on the basis of symptoms. A lack of recognition of the presence of macroPRL can lead to unnecessary laboratory investigations, imaging, and pharmacologic or surgical treatment., Conclusion: Until there is a commercially available PRL assay that is not subject to interference by macroPRL, clinicians should consider the possibility of macroPRL, especially if the clinical presentation, imaging findings, and/or response to therapy reveal inconsistencies.

Background: Metastasis to the bone is a deleterious aspect of breast cancer and is a preferred site that results in bone loss. Hormones such as prolactin (PRL) have not yet been studied for their role in modulating the secondary tumor bone microenvironment., Methods: We used quantitative immunohistochemistry with 134 samples of human primary breast cancer and 17 matched primary breast cancers and bone metastases. A Cox proportional hazards regression model was fitted to evaluate the associations between high prolactin receptor (PRLR) expression and time to bone metastasis, adjusting for estrogen receptor status, lymph node status, and chemotherapy status. We assessed osteoclast differentiation, osteoclast size, and measured pit formation in dentine slices. Statistical tests were two-sided., Results: High PRLR expression in the primary breast tumor was associated with a shorter time to metastasis that includes bone (PRLRAQUA Max-per 100 unit hazard ratio = 1.04, 95% confidence interval = 1.00 to 1.07, P = .03). We observed the PRLR in rare samples of bone metastases and matched primary breast cancer. PRL treatment of breast cancer cells induced osteoclast differentiation and bone lysis via secreted factors and was abrogated by a PRLR antagonist (delta1-9-G129R-hPRL). We demonstrated that sonic hedgehog is a PRL-regulated cytokine in breast cancer cells and part of the mechanism that induces osteoclast differentiation., Conclusions: Our evidence indicates that PRL-PRLR can escalate the impact of breast cancer on bone metastasis and that the presence of the PRLR in the tumor microenvironment of breast cancer bone metastasis has the potential to modulate the microenvironment to induce lytic osteoclast formation., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

In previous studies, our team showed that the inhibition of prolactin (PRL) secretion by the dopamine agonist quinagolide reduces milk production in dairy cows. The objective of this study was to determine the effects of administration of a dopamine antagonist on basal and milking-induced PRL concentrations in blood and on milk production during positive energy balance and feed restriction in dairy cows. Eighteen mid-lactation Holstein cows received daily s.c. injections of either domperidone (300 mg, DOMP, n=9) or the vehicle, canola oil (CTL, n=9), for 5 wk. During wk 5, all cows were fed at 65% of their dry matter intake in the previous week. Blood and milk samples were collected before (for blood) and during (for milk) the a.m. milking thrice weekly from d -9 to 41 (8d after the last injection). In addition, blood samples were collected during the a.m. milking on d -1 (before the first injection), and on d 1, 28, and 34. Basal PRL concentration was similar in both groups before the start of the treatments. Domperidone injections caused a gradual increase in basal PRL concentration. Feed restriction reduced basal PRL concentration in both the CTL and DOMP cows, but PRL concentration remained higher in the DOMP cows. Prolactin concentration remained elevated in the DOMP cows 7d after the last injection. The milk concentration of PRL increased during the DOMP treatment, but the increase was smaller than that observed in serum. In the CTL cows, the milking-induced PRL release above the premilking concentration was similar on d -1, 1, and 28 but was reduced during feed restriction. In the DOMP cows, the milking-induced PRL release was similar on d -1 and 1 but was reduced on d 28 and 34. Milk production was similar for both groups before the treatments started but was greater in the DOMP cows during the treatment period, at 2.9 ± 0.6 and 2.4 ± 0.6 kg/d greater during wk 3 and 4 of treatment, respectively. Milk production declined in both groups during feed restriction but remained higher in the DOMP cows. Milk production became similar again for both groups after the last injection. In addition, dry matter intake was increased by DOMP. These results support the hypothesis that PRL is galactopoietic in dairy cattle., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Aim: To describe a new device for the transcervical collection of amniotic fluid (AF) in patients with ruptured membranes, and to compare the concentration of proteins in fluid retrieved by transabdominal amniocentesis and the transcervical AF collector., Study Design: Paired AF samples were collected in patients with preterm prelabor rupture of membranes (PROM) (n=11) by transabdominal amniocentesis and with the transcervical AF collector (Yoon's AF Collector™). Three proteins known to have high concentrations in AF [α-fetoprotein (AFP), β-human chorionic gonadotrophin (β-hCG), and prolactin] were measured., Results: (1) There was a significant correlation between the concentrations of analytes in AF obtained by transabdominal amniocentesis and by the transcervical AF collector (r=0.94, P<0.001 for AFP; r=0.96, P<0.001 for β-hCG; r=0.72, P<0.05 for prolactin); (2) Bland-Altman plots showed no evidence of heteroscedasticity between transabdominal or transcervical AF concentrations of these markers., Conclusions: There was a strong correlation between the concentrations of proteins in AF collected by amniocentesis or with the transcervical device.

Xbp1, a key mediator of the unfolded protein response (UPR), is activated by IRE1α-mediated splicing, which results in a frameshift to encode a protein with transcriptional activity. However, the direct function of Xbp1 in epithelial cells during mammary gland development is unknown. Here we report that the loss of Xbp1 in the mammary epithelium through targeted deletion leads to poor branching morphogenesis, impaired terminal end bud formation, and spontaneous stromal fibrosis during the adult virgin period. Additionally, epithelial Xbp1 deletion induces endoplasmic reticulum (ER) stress in the epithelium and dramatically inhibits epithelial proliferation and differentiation during lactation. The synthesis of milk and its major components, α/β-casein and whey acidic protein (WAP), is significantly reduced due to decreased prolactin receptor (Prlr) and ErbB4 expression in Xbp1-deficient mammary epithelium. Reduction of Prlr and ErbB4 expression and their diminished availability at the cell surface lead to reduced phosphorylated Stat5, an essential regulator of cell proliferation and differentiation during lactation. As a result, lactating mammary glands in these mice produce less milk protein, leading to poor pup growth and postnatal death. These findings suggest that the loss of Xbp1 induces a terminal UPR which blocks proliferation and differentiation during mammary gland development., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)