Normal Prolactin Levels Research Articles

SAT-LB54 Acute Sterile Meningitis as a Primary Manifestation of Pituitary Apoplexy

Background: Pituitary apoplexy (PA) is a rare endocrinopathy that requires prompt diagnosis and treatment. Presentation with acute neutrophilic meningitis is uncommon.Clinical Case: A 67-year-old man presented to our hospital with a 2-week history of worsening bilateral frontal headache, nausea, and dry heaving. On admission, the patient was somnolent with a score of 13 on the GCS assessment (E2, V5, M6). The neurological exam was overall normal with normal ocular motion and intact cranial nerves, except for a left eye peripheral vision defect. Plain head CT revealed a well-circumscribed ovoid pituitary mass with suprasellar enlargement, consistent with a pituitary macroadenoma. Sellar MRI showed a pituitary mass, roughly 20 x 19 x 24 mm, bulging into the suprasellar cistern with optic chiasm elevation. Analysis of pituitary function revealed low ACTH concentration of 2.8 pg/mL (n = 7.2 - 63.3 pg/mL), a low random cortisol level of 1.7 ug/dL (n = 2.9 - 19.4 ug/dL), a low TSH of < 0.1 uIU/mL (n = 0.35 - 4.9 uIU/mL), a low free T4 level of 0.72 ng/dL (n = 0.77 - 1.48 ng/dL), a low LH of 0.8 IU/L (n = 1.7 - 8.6 IU/L) with a very low total testosterone level of < 3 ng/dL (n = 300 - 720 ng/dL) and normal prolactin, IGF-1 and GH levels. On hospital day 2, the patient had worsening encephalopathy with left eye ptosis and decreased vision. Repeat CT and MRI showed no interval change in the pituitary adenoma or evidence of bleeding. An immediate lumbar puncture was performed and CSF analysis revealed an increased leukocyte count of (1106/mm3) with 89% neutrophilic granulocytes, and increased total protein level of 138 mg/dL (n = 15 - 40 mg/dL), red blood cell count of 2040 without xanthochromia and glucose of 130 mg/dL (n = 40 - 70 mg/dL). Based on the laboratory results and new symptoms, empirical antibiotic (vancomycin, ceftriaxone, and ampicillin) therapy was started for suspected bacterial meningitis before the confirmation of the CSF culture study. CSF culture did not grow any organisms. Given the sudden visual impairment and neurological deterioration, the patient underwent transsphenoidal resection of the tumor with free nasal mucosal graft reconstruction. Histological examination revealed a necrotic pituitary adenoma with apoplexy and no evidence of hemorrhage. Postoperatively, his neurological exam greatly improved. His left pupil was reactive to light and the third palsy was improving.Conclusion: This case reinforces the importance of including PA in the differential diagnosis of acute headache, particularly in patients presenting with visual disturbances. Patients with PA often present with sterile meningitis due to increased debris and blood in the subarachnoid space which closely mimics acute bacterial meningitis. While MRI remains a sensitive imaging modality for the detection of PA, the latter remains a clinical diagnosis. Timely diagnosis with high clinical suspicion and treatment is essential.

MON-282 Treatment of Hyperprolactinemia with Ropinirole: An Open-Label Dose Escalation Study

PurposeTreatment of hyperprolactinemia and prolactinomas with ergoline dopamine agonists (DAs) can be complicated by intolerance and resistance. Ropinirole (ROP) is a low cost selective D2/D3 receptor non-ergot DA, approved for treatment of Parkinson’s disease and Restless Leg Syndrome, that has been shown to acutely lower prolactin levels (PRL). This study investigated the efficacy and tolerability of long-term ROP therapy in patients with hyperprolactinemia.Methods & ResultsTen healthy women (21-45 yrs) with hyperprolactinemia were treated with ROP (0.25-6.0mg/d) for 6 months in an open-label dose escalation study. Clinical and biochemical status was assessed monthly and ROP doses were up-titrated to achieve normal PRL levels, restore menses, and eliminate galactorrhea. Two subjects had macroprolactinomas, 7 had microprolactinomas, and 1 had idiopathic hyperprolactinemia. 8/10 had previously been treated with cabergoline and/or bromocriptine. 5/10 were intolerant and 1/10 was resistant to ergot DAs. Pituitary MRIs were performed at baseline and 6 months.ROP was initiated at 0.25mg QHS in 9/10 subjects. One subject with severe DA intolerance was initiated on 0.125mg QHS. Subjects reaching a total daily dose (TDD) > 2.0mg/d were transitioned to ROP extended release. At study completion, TDDs ranged from 1-6mg/d, with a median TDD of 2mg/d. Baseline PRL levels were 136 ± 49ng/ml (1.9-25ng/ml). Stable PRL normalization was achieved in 50% of subjects. Of the subjects achieving normal PRL, 4 had microadenomas and 1 had idiopathic hyperprolactinemia, and the median effective TDD was 1mg/d (1-4mg/d, range). Among those not achieving PRL normalization, PRL decreased 46 ± 5.4% (Mean ± SEM) from baseline, at a median TDD of 4.0mg/d (2-6mg/d, range). In the subject with documented resistance to ergot DAs, PRL decreased from 529 to 320ng/ml, after 3 months of ROP on the maximum dose studied (6mg/d), but rose to 690ng/ml at 6 months. During ROP treatment, menses normalized in 57%, and galactorrhea resolved in 67% of affected subjects. At study completion, tumor size was unchanged in 7/8 prolactinomas. A 20% decrease in tumor size was observed in one macroadenoma, accompanied by a 30% reduction in PRL levels. There were no changes in BP, HR, weight, renal or kidney function. Mild adverse effects (AEs) were recorded in 80% of subjects. Fatigue (60%), nausea (40%), and headache (20%) were most common. Reported AEs declined after month 1 and ROP was not discontinued due to intolerance.ConclusionThese data provide support for the efficacy of ROP in the treatment of hyperprolactinemia in patients with microprolactinomas and idiopathic hyperprolactinemia. While further study is needed, ROP treatment for hyperprolactinemia could be considered in patients with ergot DA intolerance or significant cardiac valve disease.

Reference Range of Prolactin level in Sudanese non Pregnant Women Living in Khartoum State (Pilot Study)

Background: Prolactin is synthesized by the lactotrophs, which represent approximately 15% of the tissue in the anterior lobe of the pituitary. Is secreted in pulstile fashion with 4-14 pulses per day, it is normal level about 40-530 IU/L the number of lactotrophs increases during pregnancy and lactation when the demand for prolactin is increased. The objective of this study is to assess the normal prolactin level among non-pregnant Sudanese women in Khartoum state. Methods: The study involved 20 non-pregnant Sudanese women aged between 18-35 years old in Khartoum state and the normal prolactin level was evaluated using the Immune-enzymometric Assay. Results: The Mean of prolactin level was 188.61 iu/l while the range between 92.1 to 241 iu/l with a lower maximum than international level and lower range than the local lab reference. There was significant correlation of prolactin with age, which decreased with age. Conclusion: There was a narrow range of prolactin level in this study with lower maximum value than the international prolactin level.

HYPERPROLACTINEMIA AND ANEMIA IN HEMODIALYSIS PATIENTS

Aims: To determine the relationship of prolactin (PL) levels with the frequency of anemia and the level of cardiovascular events in patients with CKD VD stage.Material and methods: A prospective cohort study included 55 patients with CKD VD stage with anemia. Serum prolactin levels were determined in all patients.Results and discussion: 24 patients (44%) had normal levels of PL, and 31 (56%) patients had elevated levels of PL. It was determined that PL had a negative correlation with hemoglobin level (r = -0.42; p = 0.01), as well as a negative correlation with albumin level (r = -0.38; p = 0.02). The frequency of cardiovascular events after 12 months. In patients with elevated levels of PL was significantly higher than in patients with normal levels of PL: 17 events (55%) vs 4 events (17%) (χ2 8.4, p = 0.004).Conclusions: The prevalence of hyperprolactinemia in our study was 56%. Elevated levels of PL are associated with lower levels of hemoglobin, lower levels of albumin and an increased frequency of cardiovascular events.

Прогностическая модель риска развития гиперпролактинемии у пациентов с шизофренией на фоне антипсихотической терапии

Использование антипсихотических средств ассоциировано с повышенным уровнем пролактина. Лекарственно-индуцированная гиперпролактинемия (ГП) имеет не только краткосрочные, но и долгосрочные последствия, которые могут серьезно повлиять на качество жизни пациента. Клинические проявления ГП включают гинекомастию, галакторею, нарушения менструального цикла, сексуальные дисфункции, бесплодие, а также значимый рост вероятности развития остеопороза и онкологических заболеваний. В развитии данного побочного эффекта антипсихотической терапии участвуют не только экзогенные, но и генетические факторы. Целью данной работы было исследование клинических и молекулярно-генетических факторов развития лекарственно-индуцированной ГП и создание прогностической модели риска развития ГП, которая в перспективе может быть использована для оптимизации и персонализации назначаемой терапии при лечении шизофрении. Исследование проведено в выборке русских, проживающих в Западно-Сибирском регионе России, больных шизофренией (n=446). Средний возраст пациентов составил 41,5 ± 13,4 года (возрастной диапазон - от 18 до 65 лет). Клиническая симптоматика оценивалась по шкалам позитивных и негативных синдромов (Positive and Negative Syndrome Scale - PANSS), общего клинического впечатления (Clinical Global Impression - CGI), оценки побочного действия (Udvalg for Kliniske Undersogelser Scale - UKU), на всех пациентов заполнялся модифицированный вариант карты стандартизированного описания больного шизофренией. На основании содержания гормона пролактина в сыворотке крови были выделены подгруппы пациентов с ГП (n=227) и с нормальным уровнем пролактина (n=219). Выполнен молекулярно-генетический анализ 88 полиморфных вариантов генов серотониновых (HTR2C, HTR3A, HTR3B, HTR6, HTR2A, HTR1A, HTR1B) и дофаминовых (DRD1, DRD2, DRD2/ANKK1, DRD3, DRD4) рецепторов, дофаминового транспортера SLC6A3, переносчика норадреналина SLC6A2, системы ферментов цитохромов P450 (CYP1A2*1F, CYP2D6*3, CYP2D6*4, CYP2C19*3, CYP2C19*17, CYP2C19*2), катехол-О-метилтрансферазы СОМТ, p-глутатион S-трансферазы GSTP1, ATXN1, KREMEN1 и пролактина PRL. Получена прогностическая модель с включением генетических маркеров «rs1176744» (HTR3B), «rs10042486» (HTR1A), «rs936461» (DRD4), «rs179997» (ATXN1), «rs1076562» (DRD2), «rs3773678» (DRD3), «rs167771» (DRD3), «rs1587756» (DRD3), «rs134655» (KREMEN1),»rs3892097» (CYP2D6*4), «rs1341239» (PRL), «rs4975646» (SLC6A3), «rs13333066» (SLC6A2), а также негенетических факторов, таких как пол, возраст и доза антипсихотика в хлорпромазиновом эквиваленте (CPZeq). Разработанную фармакогенетическую панель можно рассматривать в качестве биологического предиктора развития антипсихотик-индуцированной ГП при шизофрении до назначения фармакотерапии. The use of antipsychotics is associated with elevated prolactin levels. Drug-induced hyperprolactinemia (HP) has not only short-term, but also long-term consequences, which can seriously affect the patient’s quality of life. Clinical manifestations of HP include gynecomastia, galactorrhea, menstrual irregularities, sexual dysfunctions, infertility, as well as a significant increase in the likelihood of developing osteoporosis and cancer. Not only exogenous, but also genetic factors are involved in the development of this side effect of antipsychotic therapy. The aim of this work was to study the clinical and molecular genetic factors of the development of drug-induced HP and the creation of a prognostic model of the risk of developing HP, which in the future can be used to optimize and personalize the prescribed therapy in the treatment of schizophrenia. The study was conducted in populations of russians with schizophrenia (n = 446), living in the West Siberian region of Russia. The average age of patients was 41,5 ± 13,4 years (18 - 65 age range). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression scale (CGI), the side effect rating scale (Udvalg for Kliniske Undersogelser Scale - UKU), and a modified version of the card of a standardized description of patient with schizophrenia. Based on the results on the serum prolactin level patients were divided into subgroups: with HP (n = 227) and with normal prolactin levels (n = 219). Molecular genetic analysis of 88 polymorphic variants of serotonin receptors genes (HTR2C, HTR3A, HTR3B, HTR6, HTR2A, HTR1A, HTR1B) and dopamine receptors genes (DRD1, DRD2, DRD2 / ANKK1, DRD3, DRD4), dopamine transporter gene SLC6A3, noradrenaline transporter gene SLC6A2, genes of the cytochrome P450 enzymes (CYP1A2*1F, CYP2D6*3, CYP2D6*4, CYP2C19*3, CYP2C19*17, CYP2C19*2), gene of catechol-O-methyltransferase COMT, gene of glutathione S-transferase P (GSTP1), genes ATXN1, KREMEN1 and prolactin gene PRL was performed. A prognostic model was obtained with the inclusion of the genetic markers “rs1176744” (HTR3B), “rs10042486” (HTR1A), “rs936461” (DRD4), “rs179997” (ATXN1), “rs1076562” (DRD2), “rs3773678” (DRD3), “rs167771” (DRD3), “rs1587756” (DRD3), “rs134655” (KREMEN1), “rs3892097” (CYP2D6*4), “rs1341239” (PRL),”rs4975646” (SLC6A3),”rs1333302” (SLC6A2), as well as non-genetic factors such as gender, age and dose of antipsychotic in chlorpromazine equivalent (CPZeq). The developed pharmacogenetic panel can be considered as biological predictors of the development of antipsychotic-induced HP in schizophrenia before the appointment of pharmacotherapy.

Body self-image disturbances in women with prolactinoma.

Objective:To evaluate body dissatisfaction and distorted body self-image in women with prolactinoma.Methods:Body dissatisfaction and distorted body self-image were evaluated in 80 women with prolactinoma. All patients were in menacme, 34% had normal body mass index (BMI), and 66% were overweight. Most patients (56.2%) had normal prolactin (PRL) levels and no hyperprolactinemia symptoms (52.5%). The Body Shape Questionnaire (BSQ) was used to assess the patients’ dissatisfaction with and concern about their physical form, and the Stunkard Figure Rating Scale (FRS) was used to assess body dissatisfaction and distorted body self-image. The patients were divided according to PRL level (normal vs. elevated) and the presence or absence of prolactinoma symptoms.Results:The normal and elevated PRL groups had similar incidences of body dissatisfaction and distorted body self-image. However, symptomatic patients reported a higher incidence of dissatisfaction than asymptomatic patients. Distorted body self-image was less common among symptomatic patients.Conclusion:Symptomatic patients showed higher body dissatisfaction, but lower body self-image distortion. The presence of symptoms may have been responsible for increased body awareness. The perception of body shape could have triggered feelings of dissatisfaction compared to an ideal lean body. Therefore, a distorted body self-image might not necessarily result in body dissatisfaction in women with prolactinomas.

Giant Prolactinomas: Case Series and Review of the Literature

Giant prolactinomas are rare and constitute only 2-3% of prolactinomas. They are defined as prolactinomas greater than 4 cm in size with a prolactin level of &gt; 1,000 µg/L. Unlike prolactinomas, giant prolactinomas have a male preponderance and present a decade earlier in men as compared to women. Giant prolactinomas may present with galactorrhea, irregular periods or decreased libido. Due to their large size, they can involve surrounding brain structures and may present with hydrocephalus, dizziness, seizures, deafness, and cognitive dysfunction. Laboratory assessment may reveal a falsely low prolactin level secondary to “hook effect” which is due to saturation of the capture and detection antibodies used in the assay. Dilution of the sample would show a paradoxical increase in prolactin levels confirming the hook effect. Magnetic resonance imaging (MRI) is warranted to assess the extent of the tumor. Dopamine agonists are the treatment of choice in giant prolactinomas and lead to rapid resolution of symptoms, normalization of prolactin levels, and reduction in the size of the tumors. Refractory giant prolactinomas may be treated with surgery, temozolomide or radiotherapy. Giant prolactinomas can pose unique diagnostic and management challenges because of atypical presentations and confounding laboratory assessments. We present four cases of giant prolactinomas each presenting in a unique manner and discuss the diagnostic and management dilemmas associated with them. J Endocrinol Metab. 2020;10(6):182-189 doi: https://doi.org/10.14740/jem652

Evaluation of percentage recovery together with modified reference range in hyperprolactinemia

Abstract Objective Macroprolactinemia is an important cause of hyperprolactinemia. The aim of this study was to examine the added value of the consideration of modified reference range in determination of macroprolactinemia and true hyperprolactinemia. Materials and methods Three hundred and ninety patients with high and 131 with normal prolactin (PRL) levels were included in this study. PRL had been analyzed before and after polyethylene glycol precipitation (post-PEG PRL). Recovery percentage (R%) &lt;40% and &gt;60% had been reported as macroprolactinemia and true hyperprolactinemia, respectively. Post-PEG PRL levels were evaluated according to the modified reference range obtained from those of the normoprolactinemic subjects. Results According to the R% criterion; macroprolactinemia had been detected in 24.9% and true hyperprolactinemia in 67.4% of hyperprolactinemic patients. When the data were evaluated considering the post-PEG PRL levels according to the modified reference range; 13 (13.4%) of the 97 macroprolactinemia reports would be considered as true hyperprolactinemia and 6 (2.3%) of the 263 true hyperprolactinemia reports would be changed as macroprolactinemia. Conclusion Discrimination capacity of R% criterion for true hyperprolactinemia and macroprolactinemia is limited, and we suggest that, in accordance with R% criterion, laboratory reports should include the post-PEG PRL levels along with the modified reference range.

An observational study of pregnancy and post-partum outcomes in women with prolactinoma treated with dopamine agonists.

In women with prolactinoma medical treatment with dopamine agonists (DA) can restore fertility. A number of studies have established the safety of DA during pregnancy and the impact of pregnancy and lactation on remission of prolactinoma. However, the total number of reported cases remains modest and further evidence is needed. To evaluate the safety of DA during pregnancy and remission of prolactinoma after pregnancy and lactation. Retrospective cohort study (2002-2014) of 57 pregnancies in 47 women with prolactinoma who received DA. Neonatal and pregnancy complications were recorded. Prolactin levels and treatment data were collected at the time of diagnosis, pre-conception, during pregnancy and lactation, and post-partum (up to 114months). DA treatment was stopped a median of 4.5weeks after conception in 49 pregnancies (86%). There were 49 live births (86% of pregnancies) and six miscarriages. Six pregnancies had an adverse neonatal outcome including two with congenital malformations. Following 26% of pregnancies women achieved remission after birth or lactation, and 25% of women were in remission at last follow-up. Remission was associated with older maternal age (P=0.036), a lower prolactin level at diagnosis (P=0.037), and a smaller adenoma at diagnosis (P=0.045). Successful pregnancy and lactation is common after DA treatment for prolactinoma. Fetal exposure in the first four weeks of pregnancy appears to be generally safe. Encouragingly, post-partum and after lactation a quarter of women had a normal prolactin level without medical treatment.

SUN-448 Giant Prolactinomas: A Follow-Up of 25 Years with Dopamine Agonists

Giant prolactinomas are tumors with a large size > 4 cm and/or prolactin levels higher than 3000 ng/ml and/or highly invasive growth. Today dopamine agonists, mainly cabergoline (CAB), are the first-line choice in the treatment of these tumors. Objective: To assess the efficacy, safety and long-term follow-up of patients with giant prolactinomas treated with dopamine agonists. Methods: We retrospectively reviewed the clinical records of 20 patients with giant prolactinomas. Mean age at diagnosis was: 45.2 ± 18.9 years, 75% men. The median follow-up time was 9.05 years (1.5-25.1). At diagnosis the median prolactin level was 6,545 ng/ml (3,238-15,325), the mean maximum diameter of the tumors was 4.60 ± 1.35 cm. At diagnosis, headaches were present in 55% and hypogonadism in 85% of patients; 80% had invasive tumors and 75% had visual field (VF) impairment. Since the diagnosis, almost all patients were treated with CAB except 2, one with bromocriptine LAR and the other one with oral bromocriptine, both were switched to CAB afterwards. Results: Seventy percent of patients normalized prolactin levels, this was achieved in a median time of 7.5 months (2-26) and with a mean dose 2.14 ±1.19 mg/week of CAB. Fifty-four percent of patients reached this prolactin nadir in 2-4 months with a maximum dose < 2 mg/week. The median prolactin level in the last visit was 31.23 ng/ml (12-147). Ninety percent of patients decreased prolactin level during follow-up: 50% normalized prolactin, 25% remained with a mild hyperprolactinemia, 25% with significant hyperprolactinemia. Ninety-five percent of tumors reduced their volume, 60% evolved to empty sella, the remaining achieved a mean decrease of 3.75 cm compared to the initial size (82% of average reduction compared to the initial diameter). The VF remained normal in patients in whom it was not affected, except in 1 whose VF deteriorated because of chiasmatic ptosis; in the patients who presented VF involvement: 47% improved, 40% remained unchanged and 13% worsened. The complications during the follow-up were: Cerebrospinal fluid leak in 2 patients, chiasmatic ptosis in 1 with VF impairment, intra-tumoral hemorrhage in 1. In the follow-up only 1 patient required surgery; 4 patients died, 2 because of the tumor. In 3 (15%) patients CAB was stopped at 96-180-264 months after treatment was initiated, but in all of them CAB was reinitiated due to symptomatic hyperprolactinemia. In 16 patients the treatment could never be discontinued. Conclusions: CAB was effective in the treatment of giant prolactinomas reducing tumor size (some of them evolved to empty sella) and prolactin levels in most patients, with low-moderate doses of CAB and very few complications. In our experience of 25 years of follow-up, we have not had any patients without treatment.

MON-LB080 Change of T2-Weighted Intensity of Prolactinoma as a Predictable Value for Relapse of Hyperprolactinemia after Cabergoline Withdrawal

Background The aim of this study were to assess whether change of T2 weighted signal intensity (T2-WSI) on magnetic resonance imaging (MRI) is associated with complete remission after cabergoline withdrawal in patients with prolactinoma. Methods In a retrospective cohort study, we identified 631 patients with hyperprolactinemia and pituitary adenoma from 2005 to 2018. Of 631 patients, 35 patients who stopped the cabergoline medication were included in final analysis. The patients who maintained the cabergoline treatment for less than 1 year and stopped the medical treatment because of the pregnancy or amenorrhea were excluded in this study. We measured T2-WSI of both adenoma and normal portion of pituitary gland on the initial, 6-month follow up MRI using the Picture Archive Communication System. The patients were divided into 2 groups, based on the maintenance of normal prolactin level or relapse after withdrawal of cabergoline. We compared the T2-WSI of pituitary adenoma corrected by T2-WSI of normal tissue between remission and relapse group. Results Only 20% patients relapsed at 6(3-63) months after drug withdrawal in the 14(5-97) month follow-up period. Age (35.2 vs. 29.9 years), baseline PRL level (195.0 vs. 216.7), nadir PRL level during cabergoline treatment (4.3 vs. 3.2), duration of cabergoline treatment (38.6 vs. 34.3 months), and maximal tumor size (9.0 vs. 7.6mm) were similar between the remission and recurrence group (p > 0.05 for all). In order to see whether the change of T2-WSI between initiation of treatment and six-month follow up was different between recurrence group and remission group, we performed a one by two (signal intensity of both MRI) repeated measures analysis of variance using recurrence as a between-subject factors. Result showed that there were no significant main effect of treatment (F (1,33)=2.491, p=0.124). However, there was a significant difference of T2-WSI by treatment interaction, which means that a treatment effect was different between recur and non-recur groups (F(1,33)=4.783, p=0.036). T2-WSI in remission group was significantly decreased after 6 months of treatment (Z=2.03, singned rank=292, p=0.043), but not in recurrence group (signed rank=9, p=0.469). Conclusions In this study, the change of T2-WSI was associated with relapse of hyperprolactinemia in patients with prolactinoma after withdrawal of cabergoline. Further study is necessary for evaluating the clinical significance of T2-WSI in pituitary tumors. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Is Morning Prolactin Level Sufficient for Diagnosis of Mild Hyperprolactinemia?

Background: Taking into consideration the pulsatile secretion of prolactin, a single prolactin measurement may not be adequate to confirm abnormal prolactin level. Objectives: The present study aimed to compare prolactin serum levels in the morning and in the evening in women suspected of hyperprolactinemia. Methods: This descriptive cross-sectional study recruited women presenting to the laboratory for measurement of prolactin. In patients with symptoms of hyperprolactinemia and elevated early morning serum prolactin, a new sample was obtained in the evening. Women with a clinical history of hyperprolactinemia, pituitary adenoma and galactorrhea were excluded. Prolactin was measured by chemiluminescence method. A P value less than 0.05 was defined as statistically significant. Results: From 109 women with morning hyperprolactinemia, 52 (41.71%) had normal evening prolactin levels and 57 (58.29%) had high prolactin levels in the evening. The mean percentage of reduction in prolactin levels in the evening compared to the morning, in women with normal evening prolactin was significantly more than those who had high evening prolactin levels. Of women who had normal prolactin levels in the evening, 30.77% had normal mean levels of prolactin in the morning, as well. Conclusions: Prolactin levels of women were significantly higher in the morning than those in the evening. In 42% of the patients with borderline morning hyperprolactinemia (about twice the normal upper limit), evening prolactin levels return to normal. Therefore, single measurements may not be enough for the diagnosis of hyperprolactinemia and a criterion for treatment, particularly in the absence of galactorrhea in women with abnormal uterine bleeding.

SUPRAORBITAL CRANIOTOMY APPROACH IN ENDOCRINE-INACTIVE PITUITARY ADENOMAS

A non-functioning pituitary adenoma is one of the most common endocrine tumors with a benign pattern in the majority of cases. We present the case of a 69 years old female admitted to the endocrinology department for visual field defects, dizziness, memory disorder, bradylalia, bradypsychia. During the medical examination, the patient presented a syncopal event, with abundant sweating and temporo-spatial disorientation. Magnetic Resonance Imaging revealed a pituitary macroadenoma of 23/33.3/37 mm with two spherical lesions overlapped (“snowman” shape), with mass effect on the cavernous sinuses extending to the posterior wall of the left sphenoid sinus. Visual field examination showed significant narrowing to both eyes. The hormonal profile revealed gonadotropic insufficiency and low Insulin-like Growth Factor 1 with normal prolactin and cortisol levels. Thyroid hormonal evaluation highlighted primary hypothyroidism due to autoimmune thyroiditis. Two weeks later, adenomectomy was performed by supraorbital craniotomy. After discharge, she received the thyroid hormone replacement therapy initiated preoperatively and specific therapy for associated pathology: diabetes mellitus type 2, osteoporosis, and hyperlipidemia. Pituitary surgery is the first line treatment for the majority of patients with symptomatic endocrine-inactive adenomas. A further multidisciplinary close check-up is periodically recommended.

A study on thyroid profile and prolactin level in hypothyroid females of a rural population of a developing country

Background: In patients with primary hypothyroidism, there are increased levels of thyrotropin-releasing hormone (TRH) which can cause rise of prolactin (PRL) levels and these patients may have galactorrhea. Aims: Considering the clinical importance of hyperprolactinemia in ovulation disorders, sterility, and menstruation disorders, the present study was conducted to observe the prevalence of hyperprolactinemia and related galactorrhea in newly diagnosed hypothyroid females and correlate serum PRL level with thyroid-stimulating hormone (TSH) in hypothyroid females in a rural population of East India. Materials and Methods: This pilot study was conducted in Burdwan Medical College on 200 newly diagnosed female hypothyroid participants after taking institutional ethical clearance and informed consent of the participants. Age and gender-matched 100 controls were taken. Serum TSH, serum free thyroxine (fT4), and serum PRL levels were assessed. A questionnaire was designed for the evaluation of hypothyroidism symptoms for all the participants. These symptoms were galactorrhea, dryness of skin, feeling cold, hair loss, weakness, weight gain, constipation, loss of libido, and menstrual abnormalities. A total number of hyperprolactinemic patients were 42; out of them, 30 females were clinical and 12 were subclinical hypothyroid patients. One hundred and fifty-eight patients had normal PRL level. Results: Significant difference was found between clinical and subclinical hypothyroid females for body mass index (BMI) (P = 0.002), TSH (P

Evaluation of gonadotropin-replacement therapy in male patients with hypogonadotropic hypogonadism.

Hypogonadotropic hypogonadism (HH) is a rare disease in which medical treatment has a high success rate to achieve fertility. This study aimed to analyze the efficacy of hormone replacement therapy and determine predictive factors for successful spermatogenesis and spontaneous pregnancy in patients with idiopathic HH. A total of 112 patients with low testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and normal prolactin levels were diagnosed with HH and administered LH and FSH analogs as hormone replacement therapy. During treatment, 96 (85.7%) patients had sperm present in ejaculate samples. Among these patients, 72 were married and wanted a child. Of these 72 patients, 48 (66.7%) of couples had pregnancies from natural conception. After initiation of treatment, the mean time for the appearance of sperm in semen was 9.48 months. There were no significant differences between baseline FSH, T, and LH levels; however, older age, larger testicular size, and low rate of undescended testes were favorable factors for successful spermatogenesis. Larger testicular size and older age were also the main predictive factors for natural conception. We found that patients with undescended testes had a younger age, smaller testes, and lower T levels compared with patients exhibiting descended testes. The rate of sperm found in the ejaculate was not significantly decreased in patients with undescended compared with descended testis (73.7% vs 87.6%, P = 0.261). The medical approach for males with HH and azoospermia provides a successful treatment modality in regard to successful spermatogenesis and achievement of pregnancy.

Diagnostic value and cross-correlation interdependence of indexes of endocrine and lipid exchange at a metabolic syndrome complicated by chronic coronary artery disease and diabetes mellitus type 2

The aim of the research is to set hormonal and lipid indexes as diagnostic markers of metabolic syndrome in intercommunication with its complications, such as coronary artery disease and diabetes mellitus type 2 as the compensated and decompensated stages.Material and methods. Interdependence of endocrine and lipid exchange indexes for patients with a metabolic syndrome assotiated with chronic coronary artery disease and diabetes mellitus type 2 as the compensated and decompensated stage was studied in research. 163 patients with a metabolic syndrome were inspected. Depending on a presence or absence of the assoсiated pathology, three groups formed. The first group was represented by patients with a metabolic syndrome in combination with chronic coronary artery disease, second group — by patients with chronic coronary artery disease and compensated diabetes mellitus type 2, that arose up on a background of a metabolic syndrome. Third group was represented by patients with chronic coronary artery disease and decompensated diabetes mellitus type 2 on a background of a metabolic syndrome. The levels of cortisol, thyroid-stimulating hormone, free thyroxine, prolactin and lipid spectrum indexes were determined. Result. According to results of research, first and second groups were characterized by normal cortisol and prolactin levels and statistically significantly increased thyroid-stimulating hormone level. Statistically significantly increased cortisol and prolactin (in women) levels and the normal thyroid-stimulating hormone level were diagnosed in patients of the third group in comparison with the control and second groups. An amount of free thyroxine in patients of all groups was at the level of control values. Patients with chronic coronary artery disease and decompensated diabetes mellitus type 2 on a background of a metabolic syndrome differed from previous groups by the changes of lipid spectrum: the statistically increase of total cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol levels at the reliable decrease of high-density lipoprotein cholesterol level. The cross-correlation analysis confirmed differences between the groups of the compensated and decompensated diabetes mellitus type 2 in association with coronary artery disease on a background of a metabolic syndrome. Correlation connection between the parameters of lipid spectrum, cortisol, prolactin and by a thyroid-stimulating hormone was observed at the patients of the second group. The patients of the third group didn’t have intercommunication between these indicated indexes, correlation was educed only between a cortisol and prolactin (for women). Conclusion. Levels of prolactin, cortisol and thyroid-stimulating hormone at a metabolic syndrome change, depending on the presence of the associated diseases. The normal cortisol and prolactin levels and increase level of thyroid-stimulating hormone was educed in patients with metabolic syndrome with chronic coronary artery disease and also at a metabolic syndrome with chronic coronary artery disease and compensated diabetes mellitus type 2. Increase of cortisol and of prolactin (for women) levels at the normal level of thyroid-stimulating hormone was observed at a metabolic syndrome complicated by chronic coronary artery disease and decompensated diabetes mellitus type 2. Correlation between indexes of lipid exchange and hormonal status was educed at МС complicated by chronic coronary artery disease and compensated stage of diabetes mellitus type 2. This correlation does not appear at a metabolic syndrome with chronic coronary artery disease and decompensated diabetes mellitus type 2. Thus, the changes of the higher indicated hormones play role of diagnostic markers of decompensation of the investigated pathological processes and accompanied by the corresponding changes of lipid spectrum.

The relation of serum prolactin levels and Toxoplasma infection in humans.

BackgroundToxoplasma gondii is an intracellular protozoan parasite distributed worldwide. Although the infection is benign in immunocompetent individuals, it is life threatening and complicated in immunocompromised patients and fetuses of pregnant women who received their first exposure to T. gondii during the pregnancy. Prolactin (PRL) is a hormone that is secreted by the pituitary gland, and it is confirmed that it plays a role in the immune system. The present study was carried out to assess the possible relation between serum PRL levels and Toxoplasma infection frequency in human.MethodsIn this cross-sectional study, 343 serum samples (240 from women and 103 from men) were collected from individuals who were referred for PRL checking in laboratories of Karaj, Iran. Blood samples were collected, and sera were separated and analyzed for the detection of anti-Toxoplasma IgG antibody by ELISA method. The levels of PRL were measured by Roche Elecsys 2010 analyzer, electrochemiluminescence technology.ResultsOf 343 sera, 110 samples (32%) consisting of samples from 42 men and 68 women had anti-T. gondii IgG antibody. The prevalence of T. gondii infection in women with high PRL levels was lower than that in the comparison group with normal levels of PRL and the relationship between these two parameters was statistically significant (P=0.016). In women with hyperprolactinemia, by increasing of PRL levels, the prevalence of T. gondii infection was reduced.ConclusionThe results of the current study confirmed the previous studies based on immunoregulatory role of PRL and indicated that high levels of PRL could be related to Toxoplasma seronegativity in women.

Effect of Brexpiprazole on Prolactin

Hyperprolactinemia is an undesirable effect of most antipsychotics because of D2-receptor blockade. We assessed the effect of the D2-receptor partial agonist brexpiprazole on prolactin, based on pooled data from three 6-week, randomized, placebo-controlled studies and two open-label extension studies in patients with schizophrenia. In the short-term studies, patients received 0.25, 1, 2, 4 mg brexpiprazole or placebo; or flexible-dose brexpiprazole (2-4 mg/d), placebo, or active reference. The extension studies were 52-week, flexible-dose (1-4 mg/d) studies. We studied changes from baseline and shifts in prolactin status in patients with normal or elevated prolactin levels at baseline, and prolactin-related treatment-emergent adverse events (TEAEs). Median changes from baseline to week 6 in brexpiprazole-treated patients in short-term studies were as follows: 3.63 ng/mL (females), 0.26 ng/mL (males); placebo: -2.15 ng/mL (females), -1.08 ng/mL (males).Median changes from baseline to week 52 in long-term studies were 0.60 ng/mL (females) and 0.18 ng/mL (males). Prolactin levels in patients with baseline values greater than 1× upper limit of normal tended to decrease over time regardless of previous treatment.The proportions of brexpiprazole-treated patients with greater than 3× upper limit of normal postbaseline prolactin values in short-term studies were as follows: 1.5% (females), 1.6% (males); placebo: 3.6% (females), 3.4% (males). Corresponding figures in long-term studies were 5.3% (females) and 2.0% (males).In short-term studies, the incidence of prolactin-related TEAEs was 1.8% for brexpiprazole and 0.6% for placebo. In long-term studies, the incidence of prolactin-related TEAEs was 1.7%. Small changes in prolactin levels, low proportions of patients with postbaseline elevated prolactin values, and low incidence of prolactin-related TEAEs were observed after treatment with brexpiprazole.

Different effects of fenofibrate on cardiometabolic risk factors in young women with and without hyperprolactinemia.

Elevated prolactin levels are associated with increased cardiometabolic risk. No previous study has compared the effect of hypolipidemic therapy on plasma levels of lipids and other cardiometabolic risk factors in patients with and without hyperprolactinemia. The study included three age-, weight-, blood pressure- and lipid-matched groups of premenopausal women: 18 women with untreated hyperprolactinemia, 19 women with bromocriptine-treated hyperprolactinemia and 20 drug-naïve women with normal prolactin levels. Because of concomitant atherogenic dyslipidemia, all patients were treated with fenofibrate (200 mg daily) for 12 weeks. Plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were assessed at baseline and at the end of hypolipidemic treatment. Unlike similar baseline lipid levels, plasma concentrations of the remaining investigated cardiometabolic risk factors were higher in women with elevated prolactin levels than in patients with normal prolactin levels. The impact of fenofibrate on total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels, as well as on uric acid, hsCRP, homocysteine, and fibrinogen was less pronounced in women with untreated hyperprolactinemia than in women with bromocriptine-treated hyperprolactinemia and drug-naïve women with normal prolactin levels. The results of our study indicate that cardiometabolic effects of fenofibrate depend on plasma prolactin levels.

Long-term follow-up of female prolactinoma patients at child-bearing age after transsphenoidal surgery

Prolactinoma is the most common subtype of functional pituitary adenoma. Effective therapy is required for women of child-bearing age to achieve remission at serum prolactin level and regain reproductive function. To evaluate long-term outcomes, including menstrual recovery, after transsphenoidal surgery on female prolactinoma patients by experienced neurosurgeons. Observational study. Consecutive female prolactinoma patients aged from 16 to 45 years were included. Histological analysis after surgery revealed adenoma with positive staining for prolactin. Plurihormonal cell adenomas were excluded. Clinical manifestations, surgical indications, serum prolactin level before and after surgery, surgical complications, pituitary fuctions, drug maintenance, the status of menstruation, and pregnancy. Sixty-three consecutive female patients with a mean age of 29.5 ± 1.1 years were included. Based on magnetic resonance imaging findings before surgery, 31 (49.2%) patients had microadenoma, and the remaining 32 (50.8%) had macroadenoma. The median follow-up after transsphenoidal surgery was 53 (33-74) months, and long-term surgical remission was achieved in 50 (79.37%) patients with 28 (90.32%) microadenomas and 22 (68.75%) macroadenomas. No meningitis or persistent cerebrospinal fluid leaks occurred. Only one case suffered from persistent diabetes insipidus at follow-up. No severe pituitary dysfunction was observed in microprolactinoma patients. Of patients with menstrual disorders, 85% regained regular menstrual cycles after surgery. Nineteen patients in this cohort desired pregnancy and 15 of them successfully gave birth after surgery. All 17 microadenoma patients with modern surgical indications achieved normal prolactin levels and regular menstrual cycles with only one patient on drug therapy at follow-up. Long-term follow-up showed a high remission rate in female prolactinoma patients, especially in microadenoma patients, after surgery. Transsphenoidal surgery performed by experienced neurosurgeons may offer a valuable approach to treat female microprolactinoma patients of child-bearing age with modern indications for surgery.