Drug-induced Hyperprolactinemia Research Articles

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.

Association of raised levels of IL-4 and anti-TPO with hyperprolactinemia.

The modulatory role of prolactin in autoimmune regulation is well established. Hyperprolactinemia is often associated with autoimmune disease like systemic lupus erythematosus and autoimmune thyroid diseases. The objective was to compare levels of direct and indirect autoimmune factors in different categories of hyperprolactinemia cases and predict the direction of association between hyperprolactinemia and autoimmune factors, if any. A total of 102 hyperprolactinemia cases (>100ng/mL serum prolactin level) were included along with 24 controls. Among 102 hyperprolactinemia cases, there were 36 idiopathic cases, 19 pituitary adenoma cases, 36 drug-induced cases, and 11 cases associated with other secondary/systemic diseases (chronic renal failure, chronic hepatic failure, etc). Direct autoimmune markers, IL-2, IFN-γ, IL-4, and IL-5, were measured in serum by ELISA. Indirect autoimmune markers, anti-TPO, anti-tg, anti-CCP, VDRL, platelet count, and aPTT, were measured as per laboratory-defined protocol. Serum levels of IL-4 and anti-TPO were significantly high in idiopathic hyperprolactinemia cases. Serum IL-4 levels were also significantly high in pituitary adenoma cases, drug-induced cases, and in cases with other secondary causes of hyperprolactinemia. Serum anti-TPO levels were also significantly high in drug-induced hyperprolactinemia cases. No significant difference in autoimmune factors is observed between macroprolactinemia and true hyperprolactinemia. Serum IL-4 and anti-TPO were high in all categories of hyperprolactinemia. This suggests a possible association of hyperprolactinemia with autoimmune conditions (high IL-4 and anti-TPO), mostly subclinical. Thus, hyperprolactinemia case with serum prolactin level >100ng/mL may require long-term follow-up for the development of autoimmune disease in future.

Management of prolactinoma: a survey of endocrinologists in China.

ObjectiveTo assess the current management of prolactinoma among endocrinologists in China.MethodsAn online survey of a large sample of endocrinologists was conducted in China. The questionnaire included 21 questions related to controversial issues about the management of prolactinomas. Doctors in the endocrinology department of a university-affiliated hospital or a comprehensive secondary hospital in 12 cities from East, West, South, North and Middle China were surveyed.ResultsA total of 290 valid questionnaires were collected, and the response rate was 40%. When hyperprolactinemia occurred, 97% of the respondents would test thyroid-stimulating hormone routinely. 22% of the respondents considered that prolactin levels <100 ng/mL exclude the presence of a prolactinoma. Only 9% of the respondents believed that prolactin >250 ng/mL could occur in all the following situations as macroprolactinoma, mircoprolactinoma, macroprolactinemia and drug-induced hyperprolactinemia. Surgery was not recommended by 272 (94%) endocrinologists as the first choice for treating microprolactinomas. 58% and 92% of endocrinologists would start drug treatment for microprolactinomas and macroprolactinomas at diagnosis. 70% and 40% chose to withdraw treatment after 2–3 years of prolactin normalization in microprolactinomas and macroprolactinomas. In case of pregnancy, 57% of the respondents considered bromocriptine as choice for women patients. Drug discontinuation after pregnancy was advocated in 63% and 27% for microprolactinoma and macroprolactinoma. Moreover, 44% of endocrinologists believed that breastfeeding was allowable in both micro- and macroprolactinoma.ConclusionThis is the first study to investigate the management of prolactinomas among endocrinologists in China. We found that the current clinical treatment was not uniform. Therefore, it is necessary to strengthen the training of endocrinologists to improve clinical diagnosis and treatment practices.

Interpretation of Serum Gonadotropin Levels in Hyperprolactinaemia

Background/Aims: Hyperprolactinaemia is a common cause of amenorrhoea due to hypogonadotropic hypogonadism. Prolactin is hypothesised to impede the reproductive axis through an inhibitory action at the hypothalamus. However, limited data exist to aid the interpretation of serum gonadotropins in the context of hyperprolactinaemia. Methods: Serum gonadotropin values were reviewed in 243 patients with elevated serum monomeric prolactin due to discrete aetiologies at a tertiary reproductive endocrine centre between 2012 and 2015. The cause of hyperprolactinaemia was categorised by an experienced endocrinologist/pituitary multidisciplinary team, unless superseded by histology. The most frequently encountered diagnoses were microprolactinoma (n = 88), macroprolactinoma (n = 46), non-functioning pituitary adenoma (NFPA) (n = 72), drug-induced hyperprolactinaemia (n = 22) and polycystic ovarian syndrome (PCOS) (n = 15). Results: In patients with prolactinoma and modestly raised serum prolactin levels (< 4,000 mU/L), increasingly FSH-predominant gonadotropin values were observed with rising prolactin level, consistent with a progressive reduction in hypothalamic gonadotropin-releasing hormone (GnRH) pulsatility. Patients with prolactinoma and higher prolactin values (> 4,000 mU/L) were more likely to have a reduction in serum levels of both FSH and LH, consistent with direct pituitary gonadotrope dysfunction. Patients with macroadenoma and extremes of serum gonadotropin values (either serum FSH or LH > 8 IU/L) were more likely to have NFPA than prolactinoma. Patients with PCOS and hyperprolactinaemia had LH-predominant secretion in keeping with increased GnRH pulsatility despite a raised prolactin level. Conclusion: The pattern of gonadotropin secretion in patients with hyperprolactinaemia reflects the underlying aetiology.

Research progress of hyperprolactinemia induced by antipsychotic drugs

During the treatment of psychotic disorders it should be aware that many commonly used antipsychotic drugs have the risk of inducing hyperprolactinemia.This review focuses on the pathogenesis, clinical symptoms and treatment strategy of the antipsychotic drug-induced hyperprolactinemia. Key words: Hyperprolactinemia; Antipsychotic agents; Adverse effects

Controversial issues in the management of hyperprolactinemia and prolactinomas - An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism.

Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare. On the other hand, among patients with macroprolactinomas (MACs), artificially low PRL levels may result from the so-called "hook effect". Patients harboring cystic MACs may also present with a mild PRL elevation. The screening for macroprolactin is mostly indicated for asymptomatic patients and those with apparent idiopathic hyperprolactinemia. Dopamine agonists (DAs) are the treatment of choice for prolactinomas, particularly cabergoline, which is more effective and better tolerated than bromocriptine. After 2 years of successful treatment, DA withdrawal should be considered in all cases of microprolactinomas and in selected cases of MACs. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) is to provide a review of the diagnosis and treatment of hyperprolactinemia and prolactinomas, emphasizing controversial issues regarding these topics. This review is based on data published in the literature and the authors' experience.

Hyperprolactinemia in Children with Subclinical Hypothyroidism.

Prevalence of hyperprolactinemia in children with subclinical hypothyroidism (ScH) is not known. This study aimed to determine the occurrence and predictors of hyperprolactinemia in euthyroid children and in children with ScH and overt primary hypothyroidism (OPH). Serum prolactin levels were estimated in consecutive children <18 years of age undergoing thyroid function evaluation and diagnosed to have normal thyroid function, ScH, or OPH. Children with pituitary adenomas, secondary hypothyroidism, multiple pituitary hormone deficiency, comorbid states, and drug-induced hyperprolactinemia were excluded. From the initially screened 791 children, hormonal data from 602 children who fulfilled all criteria were analyzed. Seventy-one (11.79%) of these had ScH, and 33 (5.48%) had OPH. Occurrence of hyperprolactinemia was highest in the OPH group (51.51%), followed by ScH (30.98%) and euthyroid children (4.41%) (p<0.001). Median (25th–75th percentiles) levels for prolactin in euthyroid, ScH, and OPH children were 13.3 (9.4-17.95), 19.15 (15.97-30.12), and 28.86 (17.05-51.9) ng/mL, respectively (p<0.001). In children, prolactin levels were comparable in males and females. An age-related increase in serum prolactin was noted in euthyroid children, which was statistically significant in post-pubertal (16-18 years) children. Area under the curve for thyroid stimulating hormone (TSH) in predicting hyperprolactinemia in children was 0.758 (95% confidence interval: 0.673–0.829; p<0.001). TSH ≥4.00 mIU/L had a sensitivity of 69.4% and specificity of 77.6% in detecting hyperprolactinemia. Hyperprolactinemia is common in children with ScH and OPH. TSH ≥4.00 mIU/L has a good sensitivity and specificity in predicting hyperprolactinemia in children. More studies are needed to establish if hyperprolactinemia should be an indication for treating ScH in children.

P.3.d.043 - Association between P-glycoprotein polymorphisms and antipsychotic drug-induced hyperprolactinemia

Background: Regular therapy for schizophrenia includes maintenance antipsychotic treatment. Unfortunately, antipsychotics also have a spectrum of side effects, including metabolic, endocrine, cardiovascular, and movement disorders. One of the common side effects of these drugs is hyperprolactinemia (HPRL) [1]. This side effect is attributed to blockade of dopamine D2 receptors on the membranes of lactotroph cells within the pituitary gland. Certain antipsychotic drugs, e.g. risperidone, are more likely to induce HPRL because of relative accumulation within the adenohypophysis. The strong prolactin-elevating effect of risperidone reflects its relatively high blood/brain concentration ratio, a consequence of it being a substrate for the p-glycoprotein (P-gp, also known as ABCB1) pump [2]. Therefore, P-gp genotypes with altered functional activity might influence the potential of risperidone to cause HPRL as the changed blood/brain concentration ratio would lead to an altered vulnerability for CNS side effects like parkinsonism. Such side effects are expected to make dose adaptations necessary, which would also decrease exposure of lactrotroph dopamine D2 receptors. Aims: The present study aimed to investigate the influence of polymorphisms of the P-glycoprotein gene (ABCB1 gene) on the prevalence of antipsychotic-induced hyperprolactinemia in patients with schizophrenia. Methods: We studied the association between polymorphisms of the P-gp gene (ABCB1 gene) and antipsychotic drug-induced hyperprolactinemia in patients with schizophrenia from Siberia. Evaluation of serum prolactin was performed by ELISA using reagents set PRL Test System (USA). Genotyping was carried out on 8 polymorphic variants of the P-glycoprotein gene (rs1045642, rs2032582, rs4148739, rs28401781, rs2235040, rs9282564, rs2235015, and rs2032583). Associations between HPRL and polymorphisms of P-gp gene were established using logistic regression accounting for covariates (age, sex, duration of the disease, and CPZeq). An additive genetic model was tested and the analysis was carried out both in the total sample and in subgroups stratified by the use of risperidone/paliperidone (N = 76) or sulpiride/amisulpride (N = 13). Bonferroni correction was applied assuming 5 independent tests estimated via the correlation between the SNPs. Results: 446 Russian patients with schizophrenia were examined, including 225 women and 221 men [3]. The average age of patients was 42.1 ± 1.4 years. No statistically significant associations were obtained in the total sample after correction for multiple-testing. However, the rs2032582 variant appeared to be protective against HPRL in the subgroup of patients using risperidone or paliperidone (OR = 0.17, 95% CI = 0.04–0.79, adjusted p = 0.041). Discussion: Our finding supports the hypothesis that a variant of P-gp gene may influence the likelihood of inducing HPRL in patients using risperidone or paliperidone (i.e. 9-hydroxy-risperidone). This may be related to affecting the blood/brain concentration ratio of the risperidone moiety. In the total sample the association was significant but did not survive correction for multiple testing. Moreover, another variant, rs4148739, was associated to a larger extent than rs2032582. Hence, the variant may affect the affinity of the risperidone moiety specifically without having consequences for the binding and transport of other antipsychotic drugs. Conclusion: Rs2032582 of the P-gp is negatively associated with risperidone/paliperidone-induced HPRL, but not with HPRL induced by other antipsychotic drugs.

Morbidity and mortality in patients with hyperprolactinaemia: the PROLEARS study.

PurposeHigh serum prolactin concentrations have been associated with adverse health outcomes in some but not all studies. This study aimed to examine the morbidity and all-cause mortality associated with hyperprolactinaemia.MethodsA population-based matched cohort study in Tayside (Scotland, UK) from 1988 to 2014 was performed. Record-linkage technology was used to identify patients with hyperprolactinaemia that were compared to an age–sex-matched cohort of patients free of hyperprolactinaemia. The number of deaths and incident admissions with diabetes mellitus, cardiovascular disease, cancer, breast cancer, bone fractures and infectious conditions were compared by the survival analysis.ResultsPatients with hyperprolactinaemia related to pituitary tumours had no increased risk of diabetes, cardiovascular disease, bone fractures, all-cause cancer or breast cancer. Whilst no increased mortality was observed in patients with pituitary microadenomas (HR = 1.65, 95% CI: 0.79–3.44), other subgroups including those with pituitary macroadenomas and drug-induced and idiopathic hyperprolactinaemia demonstrated an increased risk of death. Individuals with drug-induced hyperprolactinaemia also demonstrated increased risks of diabetes, cardiovascular disease, infectious disease and bone fracture. However, these increased risks were not associated with the degree of serum prolactin elevation (Ptrend > 0.3). No increased risk of cancer was observed in any subgroup.ConclusionsNo excess morbidity was observed in patients with raised prolactin due to pituitary tumours. Although the increased morbidity and mortality associated with defined patient subgroups are unlikely to be directly related to the elevation in serum prolactin, hyperprolactinaemia might act as a biomarker for the presence of some increased disease risk in these patients.

Corynebacterium kroppenstedtii Is an Emerging Cause of Mastitis Especially in Patients With Psychiatric Illness on Antipsychotic Medication.

This retrospective study of patients with Corynebacterium kroppenstedtii infections revealed a predominance of mastitis and a potential association with psychiatric illnesses. At least one third of our patients with C kroppenstedtii mastitis had psychiatric illness, and >92% received antipsychotic medications. Drug-induced hyperprolactinemia may be an important modifiable risk factor in these patients.

Effect in antipsychotic-induced hyperprolactinemia after switching to long-acting injectable aripiprazole: A 1-year study

IntroductionAntipsychotic-induced hyperprolactinemia is associated with relevant side effects: short-term as hypogonadism, gynecomastia, amenorrhoea, sexual dysfunction and galactorrhoea; long-term as cardiovascular disease, bone demineralization and breast and prostate tumors.AimsTo evaluate the effect of switching to long-acting injectable aripiprazole on long-lasting antypsychotic-induced hyperprolactinemia.MethodsThis was a prospective observational 1-year study carried out in 125 outpatients with schizophrenia who were clinically stabilized but a switching to another antipsychotic was indicated. We measured the basal prolactine at the start of the study and 1 year after switching to long acting injecatable (LAI) aripiprazole.ResultsIn basal analytic, 48% had hyperprolactinemia (21.8–306.2 ng/mL) and 66.5% of them described side effects: 78% sexual dysfunction (72% men), 11% galactorrhoea (100% women), 5.5% amenorrhoea and 5.5% bone pain (100% women). In 48% of patients with hyperprolactinemia, the previous antipsychotics comprised: LAI-paliperidone (65,7%), oral-risperidone (7%), oral-olanzapine (6.1%), oral-paliperidone (5.2%), LAI-risperidone (4%) and others (12%). One year after switching to LAI-aripiprazole, prolactine levels were lower in all patients and in 85% prolactine levels were normalized. Overall, 72% described a clinical improvement, especially in terms of sexual dysfunction.ConclusionsSeveral studies have described an improvement of drug-induced hyperprolactinemia after switching to or adding oral aripiprazole. In our study, we observed that levels of prolactine were normalized in 85% of patients with a clinical improvement in almost all of cases. These findings suggest that switching to LAI aripiprazole may be an effective alternative for managing antipsychotic-induced hyperprolactinemia due to its partial agonism in D2 brain receptors, especially in tuberoinfundibular pathway.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Menstrual Cycle Abnormalities in Patients with Prolactinoma and Drug-induced Hyperprolactinemia.

Background and Objective:Hyperprolactinemia affects the reproductive endocrine axis; however, the degree of dysfunction may vary depending on etiology. The aim of the present study was to analyze menstrual cyclicity in patients with prolactinoma and drug-induced hyperprolactinemia (DIH).Methodology:Patients with prolactinoma and DIH were retrospectively analyzed for menstrual cyclicity at presentation and response to therapy.Results:Of 128 females with hyperprolactinemia, 58 had prolactinoma (41 microadenoma and 17 macroadenoma) and 39 had DIH. Patients with prolactinoma had higher prolactin levels and increased frequency of oligomenorrhea (77.5% vs. 46%) as compared to DIH. Patients with macroprolactinoma had more severe menstrual disturbances compared to microprolactinoma. A higher percentage of patients with microprolactinoma and DIH achieved regular menstrual cycles compared to macroprolactinoma postcabergoline treatment (85% and 90% vs. 65%). There was no correlation between time to regularization of menstrual cycles with age, menstrual cycle length, duration of menstrual irregularity, or initial prolactin level in patients with prolactinoma. Linear regression analysis showed a significant association between time to regularization of menstrual cycles with time to normalization of prolactin levels (P = 0.001).Conclusion:There is a prompt restoration of menstrual cycles in patients with microprolactinoma and DIH. Patients with macroprolactinoma have more severe menstrual disturbances and lesser frequency of cycle restoration postcabergoline treatment compared to microprolactinoma and DIH.

Psychiatric Patients with Antipsychotic Drug-Induced Hyperprolactinemia and Menstruation Disorders.

Treatment with antipsychotic drugs has been associated with hyperprolactinemia. The same antipsychotic drugs have also been associated with side effects such as menstruation disorders. The aim of this study was to evaluate the prevalence of hyperprolactinemia and menstruation disorders in women undergoing antipsychotic treatment. We performed a retrospective chart review study of psychiatric patients who underwent laboratory testing for serum prolactin (PRL) level between March 2011 and March 2015 in Ehime University Hospital. Patients presenting with and without menstruation disorders were evaluated to determine if they presented concomitant hyperprolactinemia. Patients with menstrual disorders had a significant increase in serum PRL level with a mean of approximately 90 ng/mL. Those with menstrual disorders presented increased PRL levels by 2-fold that of patients without menstrual disorder. However, there was no significant difference in the equivalent dose of chlorpromazine between these two groups. Additionally, about 70% of patients with menstrual disorders received risperidone treatment. The receiver operating characteristic curve showed that the optimal cutoff point of serum PRL level associated with the development of menstrual disorders was 60 ng/mL. Based on these results, we concluded that patients with menstrual disorders presented increased serum PRL, and that most of them underwent treatment with risperidone.

Management of prolactinomas: a survey of physicians from the Middle East and North Africa

Prolactinomas are the commonest functional tumors of the pituitary gland. There are still controversies regarding medical therapy in specific clinical situations. Patients may be managed by different specialists in the Middle East and North Africa (MENA) region and no data exist on patterns of clinical management. To ascertain the diagnostic and therapeutic approaches to prolactinomas among relevant professionals from the MENA region. An online survey of a large sample of physicians was conducted. The questionnaire covered various aspects of diagnosis and treatment of prolactinomas. 468 respondents were included; 36% were endocrinologists; 49% worked in public facilities and 81% graduated more than 10years. 40 and 30% would have seen 1-5 and more than 5 suspected or confirmed prolactinomas over a 6months period, respectively. Regarding the diagnosis, 30% of the respondents considered that prolactin levels <100ng/ml exclude the presence of a prolactinoma. 21% of respondents considered prolactin levels >250ng/ml compatible with macroprolactinomas only, whereas others accepted this to be compatible also with microprolactinomas, macroprolactinaemia and drug-induced hyperprolactinemia (50, 42 and 36% respectively). 71% of respondents favored the screening for macroprolactin in asymptomatic individuals with hyperprolactinemia. Regarding the treatment, 84% of respondents would treat microprolactinomas even in the absence of symptoms whereas 72% of the respondents would treat microprolactinomas only if symptoms exist. 60 and 49% of the respondents chose cabergoline as the drug of choice to treat macroprolactinomas and microprolactinomas respectively. Similar proportions had no preference of either cabergoline or bromocriptine as the best treatment for macroprolactinoma (27%) and microprolactinomas (32%). 46 and 75% of respondents favored treatment withdrawal 2-3years after prolactin normalization in patients with macroprolactinomas and microprolactinomas, respectively whereas 10% of respondents withdraw treatment after menopause in either case. 94% of respondents considered medical therapy as the primary treatment for microprolactinomas. In case of pregnancy, 49% considered bromocriptine as the drug of choice for women who wish to become pregnant. 65 and 38% of respondents advocated discontinuation of treatment with dopamine agonists in patients with microprolactinomas and macroprolactinomas, respectively. Finally, 48% would allow breast-feeding without restriction, 28% would restrict it to patients with microprolactinomas and 25% would not recommend it for women with prolactinomas. This is the first study of the clinical management of prolactinomas in the MENA region. Some of the practices are not in line with the latest Endocrine and Pituitary Societies guidelines. These warrant further discussions of contemporary guidelines in regional forums.

How I approach Drug-Induced Hyperprolactinaemia

How I approach Drug-Induced Hyperprolactinaemia

P.3.b.028 - Gene polymorphism of neurotransmitter transporters in schizophrenic patients with drug-induced hyperprolactinemia

The regular therapy of schizophrenia includes a maintenance antipsychotic treatment, which improves the long-term prognosis of the disease [2]. Unfortunately antipsychotics also have a spectrum of side effects, including metabolic, endocrine and movement disorders [3,4]. One of the common side effects of these drugs is hyperprolactinemia (HP) [1]. The results of pharmacogenetic studies aimed at prognostic evaluation of the safe use of antipsychotics are the most persuasive. The components of dopamine, serotonin and norepinephrine neurotransmission in schizophrenia are considered as the main target for the action of antipsychotics. The present study aims to elucidate the role of 12 SNPs of dopamine transporter gene SLC6A3, 9 SNPs of norepinephrine transporter gene SLC6A2 and polymorphism of vesicular monoamine transporter gene SLC6A2 in the pathogenesis of antipsychotic-induced hyperprolactinemia in patients with schizophrenia. A total of 445 ethnic Russian patients from Siberia regions were studied, including 224 women and 221 men with a diagnosis of paranoid schizophrenia (the mean age - 42.1±1.4 years). Prolactin level was analyzed using the AccuBind ELISA Microwells kit (Monobind Inc., USA). Genotyping of SNPs was done with The MassARRAY® Analyzer 4 by Agena Bioscience™, using SEQUENOM. Statistical analysis was performed using the SPSS program. The Hardy-Weinberg equilibrium and differences in genotype frequencies were tested using a chi-square test. Differences were considered significant at p

P.3.b.037 - Gene polymorphism of serotonin receptors and drug-induced hyperprolactinemia in schizophrenic patients

Background: Antipsychotics have been used for more than 50 years in the treatment of schizophrenia and many other psychiatric disorders. Schizophrenic patients have to take antipsychotic medication for a long time, often throughout the life [1]. Hyper prolactinemia in these patients is a common and serious side effect of therapy with atypical antipsychotics. Genes coding for serotonin receptors are considered as candidate genes responsible for the particular antipsychotic effects of neuroleptics [2]. The present study aimed to investigate the role of polymorphisms of the serotonin receptors genes (HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B, HTR6) in the pathogenesis of antipsychotic-induced hyperprolactinemia in patients with schizophrenia. Methods: 446 Russian patients with schizophrenia were examined, including 225 women and 221 men. The average age of patients was 42.1±1.4 years. Evaluation of serum prolactin performed by ELISA using reagents set PRL Test System (USA). Genotyping was carried out on 29 polymorphic variants of the serotonin receptor genes HTR1A (rs6295, rs1364043, rs10042486, rs1800042, rs749099), HTR1B (rs6298, rs6296, rs130058), HTR2A (rs6311, rs6313, rs6314, rs7997012, rs1928040, rs9316233, rs2224721, rs6312), HTR2C (rs6318, rs5946189, rs569959, rs17326429, rs4911871, rs3813929, rs1801412, rs12858300), HTR3A (rs1062613, rs33940208, rs1176713), HTR3B (rs1176744) and HTR6 (rs1805054). The SPSS software was used for statistical analysis. The Hardy-Weinberg equilibrium (HWE) of genotypic frequencies was tested by the chi-square test. Results: We studied the association between polymorphisms of relevant 5-HT receptor genes and antipsychotic drug-induced hyperprolactinemia in patients with schizophrenia from Siberia. All patients with schizophrenia were divided into two groups: those with and without hyperprolactinemia. Statistically significant results were obtained for polymorphic variants of the genes rs6312 HTR2A (χ2 = 4.685; p = 0.030), rs12858300 HTR2C, rs569959 HTR2C, which suggests the participation of these polymorphic variants in the development of hyperprolactinemia. When men and women were studied separately, only rs569959 HTR2C (χ2 = 6.284; p = 0.043) in men reached the nominal significance threshold. This finding is probably related to the X-bound character of HTR2C (i.e., men are hemizygotes). Also, we found a statistically significant association rs12858300 HTR2C (χ2 = 9.429; p = 0.002) in the female group. We did not find statistically significant association for other polymorphisms HTR1A (rs6295, rs1364043, rs10042486, rs1800042, rs749099), HTR1B (rs6298, rs6296, rs130058), HTR2A (rs6311, rs6313, rs6314, rs7997012, rs1928040, rs9316233, rs2224721), HTR2C (rs6318, rs5946189, rs17326429, rs4911871, rs3813929, rs1801412), HTR3A (rs1062613, rs33940208, rs1176713), HTR3B (rs1176744) and HTR6 (rs1805054). Though hyperprolactinemia is primarily attributed to blockade of DRD2 in the pituitary gland, the secretion of prolactin is also modulated by 5-HT. The involvement of the HTR1A, HTR2A, HTR2C, and HTR3 in the serotonergic-induced prolactin response is well documented. Conclusion: Our results indicate that genetic variants of HTR2C may have functional consequences on the modulation of prolactin secretion. Further search for genetic markers associated with the development of side effects of neuroleptic therapy, will contribute to the development of effective methods of diagnosis, correction and treatment of disease, as well as of adherence of patients with mental disorders to psychotropic therapy.

Prevalence and predictors of hyperprolactinemia in subclinical hypothyroidism

Background and aimsHyperprolactinemia has been reported in 0–57% of primary hypothyroidism. Data on hyperprolactinemia in subclinical hypothyroidism (ScH) is scant and inconsistent. This study aimed to determine the prevalence and predictors of hyperprolactinemia in ScH. MethodsConsecutive patients diagnosed to have normal thyroid function, ScH or overt primary hypothyroidism underwent serum prolactin, gonadotropins, testosterone and estradiol estimation. Patients with pregnancy, pituitary adenomas, secondary hypothyroidism, hyperthyroidism, comorbid states and drug-induced hyperprolactinemia were excluded. ResultsFrom initially screened 4950 patients, hormonal data from 2848 individuals who fulfilled all criteria were analyzed. The occurrence of hyperprolactinemia (females:males) was highest in primary hypothyroidism (42.95%:39.53%) (n=192), followed by ScH (35.65%:31.61%) (n=770) and euthyroid individuals (2.32%:2.02%) (n=1886) (P<0.001). Hyperprolactinemia in ScH with TSH 5–7.5, 7.5–10 and >10mIU/L (females: males) was 25.56%:20.73%, 49.07%:50% and 61.43%:35.71% respectively (P<0.001). Significant positive correlation between TSH and prolactin was noted in ScH and primary hypothyroidism. In females, testosterone was lowest in patients with primary hypothyroidism. In males, serum estradiol was significantly higher, and testosterone significantly lower in men with ScH and primary hypothyroidism. Regression analysis revealed serum TSH followed by free T4, to be best predictors of serum prolactin in both sexes. ConclusionHyperprolactinemia is common in ScH, especially in those with TSH>7.5mIU/L. ROC analysis confirmed that TSH≥7.51mIU/L in females and ≥8.33mIU/L in males had a sensitivity of ≈50% with a very high specificity of >90% in detecting hyperprolactinemia. Prolactin screening may be warranted in ScH with TSH>7.5mIU/L, and may form an indication for treating ScH.