Drug-induced Hyperprolactinemia Research Articles

Drug-induced hyperprolactinemia and granulomatous mastitis: a case report and literature review

Drug-induced hyperprolactinemia and granulomatous mastitis: a case report and literature review

Treatment of hyperprolactinemia in women: A Position Statement from the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and the Brazilian Society of Endocrinology and Metabolism (SBEM).

Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.

Drug-induced hyperprolactinemia: mechanism of development, features of diagnosis and treatment

One of the causes of non-tumor related hyperprolactinemia is taking a medications. Physicians of various specialties, such as cardiologists, gastroenterologists, endocrinologists, and neurologists, encounter hyperprolactinemia as a side effect of drug therapy in their practice, but it is most often observed in the practice of a psychiatrist when treating patients with psychotropic medications. Over the past few years, there has been an increase in the frequency of prescriptions of antidepressants and neuroleptics due to post-COVID-19 syndrome, anxiety and stress caused by the pandemic of a new coronavirus infection. There is also a predisposition to the development of hyperprolactinemia on the background of taking neuroleptics due to genetic features of patients. Currently, there is no established common algorithm for diagnosis and treatment of drug-induced hyperprolactinemia in the world. Based on a review of foreign and domestic literature, the article discusses in detail the mechanisms of development and various approaches to the correction of iatrogenic (drug-induced) hyperprolactinemia, assesses the prolactogenic activity of neuroleptics, and proposes algorithms for prolactin monitoring and correction of hyperprolactinemia using dopamine agonists. Often the tactics of management of such patients need to be discussed by a team of specialized physicians.

ЛЕКАРСТВЕННО-ИНДУЦИРОВАННАЯ ГИПЕРПРОЛАКТИНЕМИЯ В ПРАКТИКЕ ИНТЕРНИСТА

Hyperprolactinemia (HPRL) is one of the most common neuroendocrine syndromes which can be either a manifestation of an independent disease (pituitary tumors) or a syndrome that accompanies a number of other diseases of the hypothalamic-pituitary zone, endocrine diseases, pathology of internal organs, lesions of the central nervous system, and can also be iatrogenic (drug-induced HPRL). HPRL is more common in women but can also occur in men with various reproductive and sexual health disorders. Many drugs can cause HPRL. In order to establish the frequency of occurrence of this problem in the clinical practice of an internist, an analysis of the literature was carried out. Articles related to HPRL induced by specific types of drugs were reviewed. This review presents the current views of domestic and foreign authors on the causes and mechanisms of development of HPRL.

The Hypothalamic-Pituitary-Gonadal Axis in Men with Schizophrenia

Schizophrenia is a severe mental disorder with a chronic, progressive course. The etiology of this condition is linked to the interactions of multiple genes and environmental factors. The earlier age of onset of schizophrenia, the higher frequency of negative symptoms in the clinical presentation, and the poorer response to antipsychotic treatment in men compared to women suggests the involvement of sex hormones in these processes. This article aims to draw attention to the possible relationship between testosterone and some clinical features in male schizophrenic patients and discuss the complex nature of these phenomena based on data from the literature. PubMed, Web of Science, and Google Scholar databases were searched to select the papers without limiting the time of the publications. Hormone levels in the body are regulated by many organs and systems, and take place through the neuroendocrine, hormonal, neural, and metabolic pathways. Sex hormones play an important role in the development and function of the organism. Besides their impact on secondary sex characteristics, they influence brain development and function, mood, and cognition. In men with schizophrenia, altered testosterone levels were noted. In many cases, evidence from available single studies gave contradictory results. However, it seems that the testosterone level in men affected by schizophrenia may differ depending on the phase of the disease, types of clinical symptoms, and administered therapy. The etiology of testosterone level disturbances may be very complex. Besides the impact of the illness (schizophrenia), stress, and antipsychotic drug-induced hyperprolactinemia, testosterone levels may be influenced by, i.a., obesity, substances of abuse (e.g., ethanol), or liver damage.

Clinical Presentations of Drug-Induced Hyperprolactinaemia: A Literature Review.

Screening for drug-induced hyperprolactinaemia, a condition characterised by higher-than-normal levels of serum prolactin induced by drug treatments, requires a comprehensive understanding of the clinical presentations and long-term complications of the condition. Using two databases, Embase and MEDLINE, we summarised the available evidence on the clinical presentations and long-term complications of drug-induced hyperprolactinaemia. Clinical and observational studies reporting on drug treatments known or suspected to induce hyperprolactinaemia were included. Database searches were limited to the English language; no date or geographic restrictions were applied. Fifty studies were identified for inclusion, comprising a variety of study designs and patient populations. Most data were reported in patients treated with antipsychotics, but symptoms were also described among patients receiving other drugs, such as prokinetic drugs and antidepressants. Notably, the diagnosis of drug-induced hyperprolactinaemia varied across studies since a standard definition of elevated prolactin levels was not consistently applied. Frequent clinical presentations of hyperprolactinaemia were menstrual cycle bleeding, breast or lactation disorders, and sexual dysfunctions, described in 80% (40/50), 74% (37/50), and 42% (21/50) of the included studies, respectively. In the few studies reporting such symptoms, the prevalence of vaginal dryness impacted up to 53% of females, and infertility in both sexes ranged from 15 to 31%. Clinicians should be aware of these symptoms related to drug-induced hyperprolactinaemia when treating patients with drugs that can alter prolactin levels. Future research should explore the long-term complications of drug-induced hyperprolactinaemia and apply accepted thresholds of elevated prolactin levels (i.e., 20ng/mL for males and 25ng/mL for females) to diagnose hyperprolactinaemia as a drug-induced adverse event.Trial Registration PROSPERO International Prospective Register Of Systematic Reviews (CRD42021245259).

DRUG INDUCED HYPER PROLACTINEMIA: INTERESTING OBSERVATIONS.

Introduction: Drugs are a common cause of hyperprolactinemia. It is essential to differentiate this cause from other pathological causes which avoids unnecessary investigations.Thorough history will help us in finding the responsible drug and holding the same will be rewarding. Here we are reporting such cases of drug induced hyperprolactinemia. Methods: It was a cross-sectional observational study. Subjects were recruited from our outpatient department. Hyperprolactinemia was defined as blood prolactin levels &gt;30 ng/mL in females and &gt;24 ng/mL in males, regardless of the presence of symptoms.Serum prolactin was repeated one week after holding the suspected drug(s).Drug induced hyperprolactinemia defined,if holding of responsible drug made normalization of prolactin levels.Results: Total of 32 subjects were studied in this study with age of 35.5±10.8years.Predominantly female subjects were present with female to male ratio 5.4. Basal prolactin was 132±68.7ng/mL and after holding the drug prolactin value was 16.9±8.2. Proton pump inhibitors in combination with prokinetics were the leading cause (71.8%) and followed by multiple drug combinations (15.6%), anti-psychiatric drugs (9.3%) and oral contraceptives (3.1%). The mean prolactin in the combination of levosulpride was 176 ng/dl, whereas with domperidone it was 126 ng/dl &amp; with oral contraceptives, respiridone it was 134,151ng/dl respectively.Conclusion: Majority cases were clinically symptomatic. Among female subjects commonest presentation was galactorrhea followed by irregular menses and breast heaviness and men presented with erectile dysfunction.Contrary to common belief in our study PPI with prokinetic combination is the most common offending agent than anti-psychotic agents. Levosulpride being the most potent drug in inducing hyper prolactinemia than other agents, though the popular belief was with the Risperidone. As the utility of PPI prokinetic combination is increasing, this might replace anti-psychotic agents as most potent &amp; most common etiology for drug induced hyper prolactinemia.

Hyperprolactinemia syndrome in women: diagnosis and correction

The article is devoted to modern views on the diagnosis and treatment of hyperprolactinemia syndrome in women. Prolactinomas are the leading cause of hyperprolactinemia syndrome. The main clinical manifestations of a pathological increase in the level of prolactin are hypogonadism and galactorrhea, in some cases there are neurological symptoms, as well as psycho-emotional and asthenovegetative disorders. The publication reviews management tactics of patients with prolactinomas and pathological conditions secondary to elevated prolactin levels. Both conservative approaches to the correction of hyperprolactinemia and surgical treatment methods are described. It is noted that at present, drug therapy has priority over surgery. In the medical treatment of hyperprolactinemia, dopamine receptor agonists are used. The duration of therapy with this group of drugs is at least 2 years. The targets should be long-term normalisation of prolactin levels and a significant reduction in the size of the tumour or its absence according to the results of magnetic resonance imaging of the brain. Women with drug-resistant prolactinomas are advised to increase the dose of dopamine receptor agonists to the maximum tolerated dose before considering surgical intervention. Special attention is paid to the management of patients whose pregnancy occurred amid a pathological increase in the level of prolactin. In addition, methods for correcting drug-induced hyperprolactinemia are considered. The long list of drugs that can cause increased prolactin levels shows that the problem of hyperprolactinemia may be encountered by doctors of various specialties. The data presented in the publication are based on clinical guidelines approved by the Russian Ministry of Health and comply with the principles of evidence-based medicine.

Abstract #1165627: Risperidone induced hyperprolactinemia levels-never seen before

A common side effect of Risperidone is hyperprolactinemia in both genders, occurring in approximately 30-80% of female patients. Risperidone typically raises serum prolactin to about 45-80 ng/mL even with prolonged use. In drug-induced hyperprolactinemia, the prolactin levels rarely exceed 100 ng/mL. Here, we present a case in which the prolactin level was elevated to over 700ng/mL on risperidone without a pituitary adenoma.

Drug-Induced Hyperprolactinemia and Hyponatremia - Biological Markers of Unfavorable Evolution in Schizophrenia

Adverse reactions to psychotropic medication can be considered as risk indicators for an unfavorable evolution of patients with schizophrenia, based on particular pathogenic mechanisms that can be used in the personalized therapeutic approach. The combination of antidepressants with antipsychotic drugs in schizophrenia has a risk of synergistic action of excessive blockade of dopamine receptors, which causes hyperprolactinemia. Primary hyponatremia occurs during pregnancy and can be an important marker for signaling neurodevelopmental abnormalities, while secondary hyponatremia has a major clinical dimension and is induced by psychotropic drugs. The pathogenic mechanisms presented can be objectified by neuroimaging examinations that bring benefits in the diagnostic accuracy and re-evaluation of the therapeutic approach, especially in correlation with the severity of biological markers such as prolactin and sodium. The persistence of high prolactin and low sodium levels is an alarm signal that announces a negative evolution of the patient or a major risk of severe cardiac, metabolic, vascular or renal comorbidities. Recognition of pathogenic mechanisms of neurodevelopment, including ventriculomegaly, hyponatremia, focal cortical dysplasia, hippocampal or temporal lobe lesions, in association with a positive history of neonatal or febrile seizures, requires prophylaxis due to high risk of onset of schizophrenia in childhood. Fetal cortical dysplasia is associated with the risk of neonatal seizures. This vulnerability favors the appearance of febrile convulsions or enuresis with changes in brain structure. Enuresis may be an important marker of neurodevelopmental potential for schizophrenia. Neonatal seizures are correlated with hyponatremia and severe hypertension, which appeared in the third trimester of pregnancy, can trigger eclampsia. Neuroimaging monitoring in patients with neurodevelopmental abnormalities, hyperprolactinemia and primary or secondary hyponatremia, acquires a major importance, being able to delimit the boundary between a functional lesion, potentially reversible, with an irreversible lesion.

Determination of the frequency of hyperprolactinemia-related etiologies and the etiology-specific mean prolactin levels.

Prolactin (PRL) is a peptide hormone secreted by the anterior pituitary that provides lactation during the postpartum period. The causes of hyperprolactinemia are pituitary tumors, medications, primary hypothyroidism, polycystic ovary syndrome (PCOS), renal failure, idiopathic, and other physiological causes such as pregnancy and lactation. In this study, we aimed to investigate the prevalence of hyperprolactinemia etiologies and the mean/median prolactin levels in different etiologies. The patients admitted to our outpatient clinic between January 2009-December 2019 were retrospectively screened from our hospital database with ICD-10 codes. Four hundred patients were included in the study. 69.5% of the patients were women. Their mean age was 43.67±13.42 years, the duration of illness was 7.8±5.6 years. The most frequent causes of hyperprolactinemia were found as follows: 52.5% (n:210) prolactinoma, 7%(n:28) gonadotropinoma, 6.5%(n:26) drug-related, 6.5%(n:25) PCOS, 5.8%(n:23) idiopathic, 5%(n:20) acromegaly, 4.8%(n:19) nonfunctioning adenoma 2.3%(n:9) craniopharyngioma. Patients with gonodotropinoma were significantly older, and the patients with PCOS were significantly younger than the patients with hyperprolactinemia due to the other etiologies. Patients with prolactinoma had significantly higher prolactin levels and longer duration of the illness when compared to other etiologies of hyperprolactinemia (168.00* ng/mL (14-23500 ) [168]; 8* years (0-39 ) [5.00] years respectively, *median values, (min- max levels) and [interquartile range], respectively. There was no significant difference between prolactin levels of other etiologic groups except prolactinoma. Surprisingly, we found PCOS patients with prolactin levels greater than 100 ng/ml and acromegaly or drug-induced hyperprolactinemia with prolactin levels greater than 200 ng/ml. In our study, unlike the literature, macroprolactinemia can be seen alone or together with other pathologies. Except for macroprolactinoma, it is not possible to diagnose according to prolactin level. Similar to the literature, prolactinoma was the most common cause of hyperprolactinemia. The causes of hyperprolactinemia, in order of decreasing frequency, were determined to be gonodotropinoma, drug-related, PCOS, idiopathic, and acromegaly. The range of prolactin detected in PCOS is given as new information. It was found that the pediatric group and the adult group had a similar etiology and PRL level. A large spectrum of physiologic/ pathologic conditions increases the prolactin levels, and prolactin levels may vary from person to person. So, the serum prolactin level alone does not guide a clinical diagnosis or make a differential diagnosis.

Prevalence of Macroprolactinemia in People Detected to Have Hyperprolactinemia.

Background Macroprolactinemia is an analytic laboma encountered as a part of prolactin assay. No data are available on the burden of macroprolactinemia in Indians. This study aimed to determine the prevalence and predictors of macroprolactinemia among people with hyperprolactinemia. Methods Consecutive patients detected to have serum prolactin > 18 ng/mL as per the upper reference limit were further screened for macroprolactin by post-polyethylene-glycol (PEG)-precipitation test. Macroprolactinemia was defined as post-PEG recovery of prolactin < 40%. Results The four most common underlying etiologies for the testing of hyperprolactinemia were polycystic ovary syndrome ( n = 402; 32.71%), pituitary adenomas ( n = 318; 25.87%), drug-induced hyperprolactinemia ( n = 224; 18.23%), and infertility ( n = 126; 10.25%). A total of 1,229 patients (male:female = 191:1038) having mean age 30.46 ± 10.14 years had hyperprolactinemia, of which 168 (13.7%) were diagnosed to have macroprolactinemia. Macroprolactinemia was significantly higher in females than males (15.03 vs. 6.28%; p < 0.001). Age quartile-based analysis revealed no difference in occurrence of macroprolactinemia. Only 34 patients (2.76%) with macroprolactinemia (< 40% recovery of prolactin post-PEG precipitation) had raised prolactin levels after recovery. These patients primarily had underlying pituitary pathology. Conclusion Macroprolactinemia is not uncommon in people being tested for hyperprolactinemia. We should not hesitate to screen for macroprolactinemia in patients who have incidentally been detected to have hyperprolactinemia.

The Epidemiology of Hyperprolactinemia in A Single Tertiary Care Center: The Importance of Drug History and Role of An Endocrinologist

Introduction: The underlying causes of hyperprolactinemia differ between studies. The study aimed to determine the causes, initial signs, and treatment methods of hyperprolactinemia. Materials and Methods: Prolactin (PRL) measurement was requested from 16241 patients between January 2016 and December 2019. A total of 176 patients whose serum prolactin levels above 29.9 ng/mL in two consecutive measurements were included in this study. Electronic Health Records (EHR) of these patients were reviewed. Results: Forty-Seven (26.8%) of 176 patients had a prolactinoma. Among the prolactinoma group, 63.8% of the patients had microadenoma. Polycystic Ovary Syndrome (PCOS)(29.5%), drugs (20.9%), and pituitary disorders other than prolactinoma (13.2%) were the most common causes of hyperprolactinemia in the non-prolactinoma group. Galactorrhea (38.3%) was the most common initial sign. Cabergoline's starting dose in the Endocrinology clinic was 1 mg/week, and 87.2% of the cases started with a 1 mg/week dose. All of the other cases (12.8%) who were diagnosed by other departments received inappropriate doses of cabergoline. Conclusions: Drug-induced hyperprolactinemia may be much more common than previously thought. Referring these patients to the Endocrinology clinic will be much more beneficial to determine both the correct dosage of cabergoline and the cause of hyperprolactinemia.

Association between 8 P-glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia.

IntroductionHyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P‐glycoprotein. Genetic variants of P‐glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland.AimsTo investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug‐induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics.MethodsIn total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross‐sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene‐polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone.ResultsWe did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic‐induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone‐induced hyperprolactinaemia.ConclusionThis study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone‐induced hyperprolactinaemia.

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.

A case of telogen effluvium associated with drug-induced hyperprolactinemia.

A case of telogen effluvium associated with drug-induced hyperprolactinemia.

New approaches to pharmacogenetics of drug-induced hyperprolactinemia in patients with schizophrenia

The pathogenesis of the development of drug-induced disorders while taking antipsychotic drugs is not well understood. The aim of the work is to study polymorphic variants of the multidrug resistance protein gene and genes encoding the metabolism and synthesis of dopamine and serotonin enzymes in antipsychotic-induced hyperprolactinemia in schizophrenia patients. As a result of a comprehensive study of 446 patients with schizophrenia and genotyping of 25 polymorphic variants of the MDR1, COMT, MAO-A, MAO-B, TPH1 and TPH2 genes, associations of polymorphisms rs1045642, rs2032582, rs4148739 (MDR1), rs6323 (MAO-А), rs1799836 (MAO-B) were revealed with the development of hyperprolactinemia. Further research is needed to develop personalized approaches to therapy.

Clinical Course of Nonfunctional Pituitary Microadenoma in Children: A Single-Center Experience.

Pituitary lesions consistent with microadenomas are increasingly discovered by MRI. Sparse data are available on the long-term clinical and imaging course of such lesions in children. The aim of this study was to define the clinical and imaging course of pituitary lesions representing or possibly representing nonfunctioning microadenomas in children to guide clinical management. Retrospective observational study. The clinical data warehouse at a tertiary care academic children's hospital was queried with the terms "pituitary" AND "microadenoma" and "pituitary" AND "incidentaloma." The electronic health records of the identified subjects were reviewed to extract data on the clinical and imaging course. A total of 78 children had nonfunctioning pituitary lesions incidentally discovered during clinical care, of which 44 (56%) were reported as presumed or possible microadenomas. In the children with microadenoma (median age 15 years, interquartile range 2), a majority (70%) underwent imaging for nonendocrine symptoms, the most common being headache (n = 16, 36%). No significant increase in the size of the microadenoma or cysts or worsening of pituitary function was seen over the average clinical follow-up of 4.5 ± 2.6 years. Four cases of drug-induced hyperprolactinemia resolved with discontinuation of the offending medication. Asymptomatic pituitary lesions representing cysts, microadenomas, or possible microadenomas follow a benign course in children. In the absence of new endocrine or visual symptoms, repeat MRI may not be needed, and if performed, should be done in no less than a year. When possible, it is prudent to discontinue hyperprolactinemia-inducing medications before imaging.

Clinical and Laboratory Characteristics of Hyperprolactinemia in Children and Adolescents: National Survey

Objective:We aimed to report the characteristics at admission, diagnosis, treatment, and follow-up of cases of pediatric hyperprolactinemia in a large multicenter study.Methods:We reviewed the records of 233 hyperprolactinemic patients, under 18 years of age, who were followed by different centers. The patients were divided as having microadenomas, macroadenomas, drug-induced hyperprolactinemia and idiopathic hyperprolactinemia. Complaints of the patients, their mode of treatment (medication and/or surgery) and outcomes were evaluated in detail.Results:The mean age of the patients with hyperprolactinemia was 14.5 years, and 88.4% were females. In terms of etiology, microadenomas were observed in 32.6%, macroadenomas in 27%, idiopathic hyperprolactinemia in 22.7% and drug-induced hyperprolactinemia in 6.4%. Other causes of hyperprolactinemia were defined in 11.3%. Common complaints in females (n=206) were sorted into menstrual irregularities, headaches, galactorrhea, primary or secondary amenorrhea and weight gain, whereas headache, gynecomastia, short stature and blurred vision were common in males (n=27). Median prolactin levels were 93.15 ng/mL, 241.8 ng/mL, 74.5 ng/mL, 93.2 ng/mL, and 69 ng/mL for microadenomas, macroadenomas, idiopathic hyperprolactinemia, drug-induced hyperprolactinemia, and other causes of hyperprolactinemia, respectively. Of 172 patients with hyperprolactinemia, 77.3% were treated with cabergoline and 13.4% with bromocriptine. 20.1% of the patients with pituitary adenomas underwent pituitary surgery.Conclusion:We present the largest cohort of children and adolescents with hyperprolactinemia in the literature to date. Hyperprolactinemia is more common in females and cabergoline is highly effective and practical to use in adolescents, due to its biweekly dosing. Indications for surgery in pediatric cases need to be revised.

MON-427 An Interesting Case of Drug-Induced Hyperprolactinemia in a Patient Who Presented with Psychosis

Background: Hyperprolactinemia is a condition characterized by excess prolactin concentration exceeding the upper limit of normal. Prolactin is a peptide hormone secreted solely by the lactotroph cells of the pituitary gland. Hyperprolactinemia may be caused by several physiological and pathological conditions most common of which is benign tumor of the pituitary gland. It is very important to differentiate this cause from other pathological causes of hyperprolactinemia. Medication use is a common cause of hyperprolactinemia. We present a case of hyperprolactinimia due to antipsychotic use in a patient who presented with psychosis. Clinical case: We present a case of a 67 Y/O female who presented to our hospital from a nursing home with altered mental status. Her medical history was remarkable for hypertension, paranoid schizophrenia and ESRD on dialysis. She was admitted to the hospital for further evaluation and was noted to have bilateral mastoiditis and acute exacerbation of paranoid schizophrenia. In view of altered mental status TSH was checked which was low and she was noted to have elevated Free T4. Endocrinology was consulted for hyperthyroidism. She was started on methimazole for hyperthyroidism. Also patient was noted to have elevated prolactin level with level as high as 729 ng/ml on admission. In view of hyperprolactinemia MRI brain was done which did not show any evidence of pituitary adenoma. On review of medications it was noted that patient was on perphenazine and olanzapine for paranoid schizophrenia. It was concluded that patients hyperprolactinemia was due to medications which included antipsychotics. Psychiatry was consulted and her antipsychotics were discontinued and she was started on antipsychotics which did not have any effect on prolactin level. After discontinuing the medication her prolactin level came down to 135 ng/ml on the day of discharge. Conclusion :This is an unusual presentation of drug induced hyperprolactinemia in patient on antipsychotics. Most of the drugs do not cause an elevation of prolactin level more than 100 ng/ml with antipsychotics causing elevation upto 300 or even 400 ng/ml. This patient did have a prolactin level of 729 ng/ml with negative MRI which is not very common.