Antipsychotics-related hyperprolactinaemia among patients with schizophrenia in Maiduguri.

Background: Hyperprolactinaemia among patients on antipsychotic medications is generally overlooked due to lack of outwardly visible symptoms, patient resistance to reporting because the symptoms are perceived as shameful, or to clinician's insufficient knowledge. Aim: The study aimed to evaluate the patterns and correlates of hyperprolactinemia among patients with schizophrenia on antipsychotic medications. Setting: The study was conducted in a psychiatric facility in Maiduguri, Northeastern Nigeria. Methods: A total of 209 patients with schizophrenia were evaluated through a cross-sectional design and assayed for serum prolactin with ELISA Kits. Frequencies and percentages were tabulated for categorical variables. Variables with significant associations with hyperprolactinaemia on chi-square (p < 0.05) were subjected to logistic regression analysis. Results: The prevalence of hyperprolactinaemia was 45.9% in all patients on antipsychotic medication. The prevalence because of the use of typical and atypical antipsychotics was 51.5% and 25.0%, respectively. Hyperprolactinaemia was significantly associated with typical antipsychotics (ß = 0314, p = 0.002), high overall drug dosage (ß = 2.340, p = 0.003), high-dose typical antipsychotics (ß = 3.228, p = 0.000), twice daily dosing frequency (ß = 2.751, p = 0.001) and polypharmacy (ß = 1.828, p = 0.0024). Conclusion: The findings support that patients on typical, high-dose antipsychotic medications and polypharmacy have a high prevalence of hyperprolactinaemia. As hyperprolactinaemia is often undetectable, screening and patient psycho-education on the significance of the signs and symptoms of hyperprolactinaemia is required for necessary clinical intervention. Contribution: The study provides evidence for the rational use of antipsychotic medications in sub-Saharan Africa.

Acute retinal pigment epitheliitis during treatment of hyperprolactinaemia.

BACKGROUND: Acute retinal pigment epitheliitis (ARPE) is a rare, idiopathic and self-limiting disease. The article aims to present ARPE in a patient using D2 dopamine receptor agonists for the treatment of hyperprolactinemia. CASE PRESENTATION: A 28-year-old female during hyperprolactinaemia treatment suffered from a dyschromatopsia and a central visual field defect in the left eye. She noticed a deterioration of vision and discontinued the cabergoline administration. The woman had not been diagnosed with other chronic conditions and exhibited no symptoms of infection. Upon admission, the patient was subjected to a test for COVID-19, which was negative. The ophthalmological examination revealed a decrease in visual acuity to distance in the left eye, which amounted to 18/20 on the Snellen chart. A central scotoma was noted on the Amsler chart and a loss of pigment epithelium was visible on the fundus of the left eye. Fluorescein angiography showed a discrete window defect in the left one, with no signs of leakage. Optical coherence tomography (OCT) scans of the maculae revealed a characteristic change in the photoreceptor layer and retinal pigment epithelium (RPE) in the fovea in the left eye. The electrophysiological tests revealed decreased function of cells in macular region. A magnetic resonance imaging (MRI) of the head and orbits demonstrated an asymmetric pituitary gland without chiasm compression and discrete signal enhancement from the left optic nerve. The patient underwent observation during hospitalisation. She reported improved colour vision and a decreased scotoma in the centre of her visual field. In regular outpatient follow-ups, successive improvements in visual acuity, as well as a decreased RPE damage and outer photoreceptor layer loss during an OCT test were observed. CONCLUSIONS: A case of ARPE is reported in a patient taking medications for hyperprolactinemia. The role of dopamine receptor antagonists in the photoreceptor function and causation of ARPE needs further evaluation.

Vitex agnus castus effects on hyperprolactinaemia.

Background: Vitex agnus castus (VAC), also known as chaste tree, is a plant from the Mediterranean area, Crimea, and central Asia. Its fruit has been used for more than 2500 years as phytotherapic agent. In the last century, VAC has been mostly used for the treatment of premenstrual syndrome (PMS), menstrual irregularities, fertility disorders, and symptoms of menopause. Since some degree of hyperprolactinaemia may be observed in patients with such disorders, VAC effects on hyperprolactinaemia have been assessed in a small number of studies and in some patient series or single case reports. It has been postulated that the diterpenes contained in VAC extract may interact with dopamine D2 receptors (D2R) and inhibit prolactin release via dopamine D2R activation in the anterior pituitary. Most of the published papers focus on the use of VAC for the management of PMS or infertility. However, due to its action on D2R, VAC could have a role in the treatment of mild hyperprolactinaemia, including patients with idiopathic hyperprolactinaemia, microprolactinoma, drug-induced hyperprolactinaemia, or polycystic ovary syndrome. Methods: We have reviewed and analysed the data from the literature concerning the use of VAC extracts in patients with hyperprolactinaemia. Results: Some evidence suggests a possible role of VAC for the management of hyperprolactinaemia in selected patients, though in an inhomogeneous way. However, there are not any large randomized controlled trials supporting the same and the precise pharmacological aspects of VAC extract in such a clinical setting still remain obscure. Conclusion: It appears that VAC may represent a potentially useful and safe phytotherapic option for the management of selected patients with mild hyperprolactinaemia who wish to be treated with phytotherapy. However, larger studies of high quality are needed to corroborate it.

Physical health monitoring for people with schizophrenia.

Schizophrenia is a severe psychiatric disorder associated with significant comorbidities and early mortality. People with schizophrenia have a greater predisposition to the top 6 modifiable global mortality (cardiometabolic) risk factors as defined by the World Health Organization (compared with the general population). These are driven by genetic, lifestyle and disease factors, and obesogenic antipsychotic medications. Smoking, obesity and type 2 diabetes are the most important modifiable cardiometabolic risk factors for cardiovascular disease in people with schizophrenia. Enhanced physical health screening, especially for cardiometabolic risk factors, is recommended for people with schizophrenia. A multidisciplinary holistic approach is recommended for treating people with schizophrenia, using contact with primary care practitioners to review their physical health.

An unusual concomitance of acute heart failure: prolactinoma in a patient with left ventricular dysfunction-a case report.

Background: Heart failure concomitant with prolactinoma is extremely rare. Case summary: We present the case of a 29-year-old man who had acute decompensated heart failure concomitant with visual loss in his right eye. Transthoracic echocardiography indicated severely decreased left ventricular (LV) function. A massive tumour on the sella turcica was detected by brain computed tomography. The findings of the laboratory tests showed hyperprolactinaemia with hypopituitarism, and the antigen test for coronavirus disease 2019 was positive as an incidental finding. Medication for heart failure and cabergoline therapy were started immediately. His LV function significantly improved, and he had no symptoms after a year. Discussion: Prolactinoma in men, which can cause visual loss and hypopituitarism, is frequently substantial when diagnosed. The cardiac manifestation of prolactinoma is uncommon. It is believed that a major contributing component to the pathogenesis of peripartum cardiomyopathy is hyperprolactinaemia. Hyperprolactinaemia may cause endothelial damage and cardiomyocyte dysfunction, eventually resulting in LV dysfunction. The success of LV reverse remodelling may be significantly impacted by heart failure and hormone treatments. Heart failure and endocrine therapy should be administered concurrently to patients who have prolactinoma and congestive heart failure.

Hyperprolactinaemia is common in Chinese premenopausal women with breast diseases.

Purpose: Hyperprolactinaemia has been proposed to play a role in breast lesions pathophysiology. Thus far, controversial results have been reported for the relationship between hyperprolactinaemia and breast lesions. Moreover, the prevalence of hyperprolactinaemia in a population with breast lesions is scarcely reported. We aimed to investigate the prevalence of hyperprolactinaemia in Chinese premenopausal women with breast diseases, and explore the associations between hyperprolactinaemia with different clinical characteristics. Methods: This was a retrospective cross-sectional study performed in the department of breast surgery of Qilu hospital of Shandong University. Overall, 1,461 female patients who underwent the serum prolactin (PRL) level assay before breast surgery from January 2019 to December 2020 were included. Patients were divided into two groups: before and after menopause. Data were analyzed using SPSS 18.0 software. Results: The results showed an elevated PRL level in 376 of the 1,461 female patients with breast lesions (25.74%). Furthermore, the proportion of hyperprolactinemia among premenopausal patients with breast disease (35.75%, 340/951) was significantly higher than among postmenopausal patients with breast disease (7.06%, 36/510). In premenopausal patients, the proportion of patients with hyperprolactinaemia and the mean serum PRL level were significantly higher in those diagnosed with fibroepithelial tumours (FETs) and in younger patients (aged < 35 years) than in those with non-neoplastic lesions and in those aged ≥ 35 years (both p < 0.05). Especially, the prolactin level exhibited steady ascending tendency for positive correlation with FET. Conclusion: Hyperprolactinaemia is prevalent in Chinese premenopausal patients with breast diseases, especially in those with FETs, which implies a potential association, to some extent, between the PRL levels in various breast diseases.

Identification of prolactin receptor variants with diverse effects on receptor signalling.

The prolactin receptor (PRLR) signals predominantly through the JAK2-STAT5 pathway regulating multiple physiological functions relating to fertility, lactation, and metabolism. However, the molecular pathology and role of PRLR mutations and signalling are incompletely defined, with progress hampered by a lack of reported disease-associated PRLR variants. To date, two common germline PRLR variants are reported to demonstrate constitutive activity, with one, Ile146Leu, overrepresented in benign breast disease, while a rare activating variant, Asn492Ile, is reported to be associated with an increased incidence of prolactinoma. In contrast, an inactivating germline heterozygous PRLR variant (His188Arg) was reported in a kindred with hyperprolactinaemia, while an inactivating compound heterozygous PRLR variant (Pro269Leu/Arg171Stop) was identified in an individual with hyperprolactinaemia and agalactia. We hypothesised that additional rare germline PRLR variants, identified from large-scale sequencing projects (ExAC and GnomAD), may be associated with altered in vitro PRLR signalling activity. We therefore evaluated >300 previously uncharacterised non-synonymous, germline PRLR variants and selected 10 variants for in vitro analysis based on protein prediction algorithms, proximity to known functional domains and structural modelling. Five variants, including extracellular and intracellular domain variants, were associated with altered responses when compared to the wild-type receptor. These altered responses included loss- and gain-of-function activities related to STAT5 signalling, Akt and FOXO1 activity, as well as cell viability and apoptosis. These studies provide further insight into PRLR structure-function and indicate that rare germline PRLR variants may have diverse modulating effects on PRLR signalling, although the pathophysiologic relevance of such alterations remains to be defined.

Comparative Study of Extrapyramidal Side Effects, Sexual Dysfunctions and Hyperprolactinaemia Using Typical and Atypical Antipsychotic Medications Among Patients with Schizophrenia in Maiduguri.

Background: Extra-pyramidal side effects, sexual dysfunctions and hyperprolactinaemia are major side effects with the use of antipsychotic medications that impede treatment adherence leading to relapse, increased cost of care and rehospitalization among patients with schizophrenia on antipsychotic medications. The study aims to compare the prevalence of extra-pyramidal side effects (EPSE), sexual dysfunctions (SD) and hyperprolactinaemia (HPRL) among patients with schizophrenia spectrum disorders on typical and atypical antipsychotic medications. The secondary aim is to determine if any associations exist between extra-pyramidal side effects, sexual dysfunctions and hyperprolactinaemia. Methodology: A cross-sectional hospital-based survey involving 209 patients with schizophrenia were interviewed with structured instruments for the assessment of sexual dysfunction, EPSE and the estimation of serum prolactin was done using Enzyme-linked Immunosorbent Assay. Frequencies and Chi-square analysis were used to compare differences in EPSE, SD & HPRL. Results: The study revealed non-statistically significant differences as a group between typical and atypical antipsychotic medication in terms of extra-pyramidal side effects, sexual dysfunction and hyperprolactinaemia. However, a significant association was observed when individual drugs were compared with haloperidol causing the highest frequency of hyperprolactinaemia (χ 2 = 14.9, P = 0.011). A significant relationship between sexual dysfunction and hyperprolactinaemia, sexual dysfunction and extra-pyramidal side effects as well as extra-pyramidal and hyperprolactinaemia was found when individual items for sexual functionin were used. Conclusion: The significant relationships between sexual dysfunction only in the domains of sexual desire and arousal with hyperprolactinaemia and extrapyramidal side effects as well as hyperprolactinaemia with extrapyramidal side effects point to a common anti-dopaminergic activity of antipsychotics via different pathways. Prospective studies among a larger sample of patients with schizophrenia are needed to unfold these relationships.

Causes of hyperprolactinaemia in the primary care setting: How to optimise hyperprolactinaemia management.

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

Sociodemographic and clinical characteristics related with hyperprolactinaemia in psychiatric clinical population.

BACKGROUND: Hyperprolactinaemia (HyperPRL) induced by psychotropic drugs is a high-prevalence consequence which has repercussions in psychical and mental health in the psychiatric population, so this research had the objective to expand which sociodemographic and clinical features are associated with prolactin (PRL) elevation in patients treated with antidepressant and/or antipsychotic drugs. METHODS: An observational, cross-sectional, comparative and retrolective study was conducted on 300 patients who received clinical attention in a third level of psychiatric care unit in Mexico during 2017. These patients have been reported to show PRL levels greater than 25 ng/mL among women and greater than 20 ng/mL among men. In the same way, sociodemographic and clinical variables were collected, as well as psychiatric diagnosis and type of psychopharmacological treatment used by the patients. RESULTS: HyperPRL was more frequent in women (80.7%) than men (19.3%). The mean levels of PRL were 68.94 ± 62.28 ng/mL with higher levels in women (71.9 ± 67.3, p=.02). Regarding the treatment, 78.3%, 71.3% and 49.7% consumed antipsychotics, antidepressants, and both drugs, respectively. The relationship between hyperPRL (>100 n/mL) and typical antipsychotics was dose-dependent (33.23 ± 13.24 mg, p=.01). In the multivariate regression models according to the type of treatment, as well as the demographic and clinical features, hyperPRL was associated independently with the use of antipsychotic treatment, pituitary adenoma and hypertension (R2=0.05). CONCLUSIONS: HyperPRL is a complex clinical syndrome frequent in the psychiatric population with detrimental long-term consequences, as well as its relationship with the use of psychotropic drugs as in the case of antipsychotics. Effective actions should be implemented in the prevention, approach and treatment of this condition paying special attention to the accompanying medical comorbidities.

Withdrawal of dopamine agonist treatment in patients with hyperprolactinaemia: A systematic review and meta-analysis.

OBJECTIVE: To estimate the proportion of patients with persistent normoprolactinaemia following dopamine agonist (DA) withdrawal and to identify predictors of successful withdrawal in patients with hyperprolactinaemia. DESIGN, PATIENTS, AND MEASUREMENTS: A systematic review of observational eligible studies were identified by searching PubMed and Embase. The primary outcome was the proportion of patients with normoprolactinaemia after cessation of DA treatment. Secondary outcome included the proportion of patients with normoprolactinaemia after DA withdrawal using individual patient data. Risk of bias was assessed by using Newcastle-Ottawa Scale. Pooled proportions were estimated using a random effects model in case I2 ≤ 75% or by reporting range of effects if I2 > 75%. RESULTS: Thirty-two observational studies enroling 1563 patients were included. The proportion of patients with persistent normoprolactinaemia ranged from 0% to 75% (I2 = 84%). Heterogeneity was partly explained by age with more successful withdrawal in patients of higher age. Individual patient data analyses suggested that the proportion of patients with persistent normoprolactinaemia 6 months after DA withdrawal with a low maintenance dose and full regression of the prolactinoma was 87.7% (95% confidence interval [CI] = 60.7-97.1; I2 = 0%) and 58.4% (95% CI = 23.8-86.3; I2 = 75%) for microadenomas and macroadenomas, respectively. CONCLUSIONS: The proportion of patients with persistent normoprolactinaemia following DA withdrawal treatment varied greatly, partly explained by the mean age of participants of the individual studies. Individual patient data analysis suggested that successful withdrawal was likely in patients with full regression of prolactinomas using a low maintenance dose before cessation.

[Prolactin and its receptor: From animal models to pituitary pathophysiology]. / La prolactine et son récepteur : Des modèles animaux à la physiopathologie hypophysaire.

Prolactin (PRL) is a polypeptide hormone that is mainly synthesized and secreted by lactotroph cells of the anterior pituitary gland. The actions of prolactin are mediated by its transmembrane receptor, PRLR. The principal role attributed to PRL is to stimulate the proliferation and differentiation of the mammary cells required for lactation, but studies of animal models have assigned more than 300 separate actions to this hormone in various species. Hyperprolactinaemia is the prototypical pathological state associated with this hormone. Indeed, hyperprolactinaemia is the most common cause of amenorrhoea due to hypogonadotropic anovulation and is one of the most prevalent endocrine causes of infertility in women. In recent years, the study of conditional or complete Prlr -/- mouse models had improved the understanding concerning the regulation of gonadotroph and lactotroph axes. It is now demonstrated that prolactin exerts autocrine or paracrine actions on lactotroph cells in vivo. One of the major advances was to better understand, using mouse models, the impact of hyperprolactinemia on gonadotroph axis. It is now accepted that hypogonadotropic hypogonadism in patients with hyperprolactinemia is mediated by a decrease of hypothalamic kisspeptin secretion. Gonadotroph axis can be restored by intravenous administration of kisspeptin. However, the mechanisms of lactotroph tumorigenesis in Prlr -/- animals remain incompletely understood and transposable to the human species, since the only patient with biallelic PRLR loss-of-function mutation leading to complete prolactin resistance that has been described so far did not have pituitary adenoma visible on MRI.

Title: La prolactine et son récepteur : Des modèles animaux à la physiopathologie hypophysaire. Abstract: La prolactine (PRL), hormone de la lactation par excellence, est majoritairement synthétisée et sécrétée par les cellules lactotropes de l'antéhypophyse. Ses actions sont médiées par le récepteur transmembranaire de la prolactine (PRLR). Alors que plus de 300 fonctions différentes ont été attribuées à cette hormone selon les espèces, son rôle chez l'Homme reste limité au développement de la glande mammaire et à l'allaitement. Les pathologies en lien avec la PRL sont essentiellement celles rencontrées en cas d'hypersécrétion de cette hormone. En effet, l'hyperprolactinémie entraîne l'altération du fonctionnement de l'axe gonadotrope chez l'homme comme chez la femme. Ainsi, l'hyperprolactinémie est une étiologie fréquente d'hypogonadisme hypogonadotrope acquis et l'une des principales causes d'anovulation et d'infertilité chez la femme. Ces dernières années, les études de modèles murins invalidés pour le PRLR, de manière globale ou conditionnelle dans l'hypophyse, ont permis d'apporter de nouveaux éléments dans la compréhension de la régulation des axes gonadotrope et lactotrope. Il est maintenant démontré que la prolactine exerce des actions autocrines ou paracrines sur les cellules lactotropes in vivo. Une des avancées majeures a été de mieux comprendre, à l'aide des modèles murins, l'impact de l'hyperprolactinémie sur l'axe gonadotrope. C'est ainsi qu'il a pu être établi que, comme chez les rongeurs, l'hypogonadisme hypogonadotrope chez les patientes atteintes d'hyperprolactinémie est médié par un déficit de sécrétion de kisspeptine hypothalamique, et que l'axe gonadotrope peut être restauré par l'administration intraveineuse de kisspeptine. Les mécanismes de tumorigenèse lactotrope des animaux Prlr −/− restent cependant incomplètement compris et transposables dans l'espèce humaine, puisque, jusqu'à présent, l'unique patiente porteuse d'une mutation bi-allélique perte de fonction du PRLR ayant fait l'objet d'une publication présentait une imagerie hypophysaire sans anomalie.

Hyperprolactinemia and insulin resistance.

Hyperprolactinaemia is the most common dysfunction of the hypothalamic-pituitary axis and occurs more commonly in women. The prevalence of hyperprolactinaemia ranges from 0.4% in the general adult population to as high as 9-17% in women with reproductive diseases. It is accompanied by the phenomenon of insulin resistance (IR), which is also a significant clinical problem nowadays. The prevalence of IR is increasing, particularly in developing countries and in younger populations, with estimates of prevalence ranging from 20 to 40% in different populations. The aim of our review is to summarize recent data on the possible association between IR and hyperprolactinaemia. This review is based on an electronic search of the literature in the PubMed database published from 2000 to 2022 using combinations of the following keywords: IR, hyperprolactinemia or IR and hyperprolactinemia. The references included in previously published review articles were also checked, and any relevant papers were also included. Numerous scientific studies have shown a relationship between IR and hyperprolactinaemia. Increased plasma prolactin (PRL) levels are often associated with an increase in tissue resistance to insulin. There are many scientific theories explaining the probable mechanisms of this phenomenon. One is the finding that glucose and PRL act synergistically in inducing the transcription of insulin genes. It is also suggested that PRL may act as a regulator of insulin sensitivity and metabolic homeostasis in adipose tissue. The topic of the mutual correlation of hyperprolactinaemia and IR is important, and it certainly requires further research and observation.

Presenting symptoms and endocrine dysfunction in Rathke cleft cysts - a two-centre experience.

INTRODUCTION: Rathke cleft cysts (RCC) arise as developmental abnormalities of the pituitary gland and are usually diagnosed incidentally. However, they may present with headaches, visual impairment, or pituitary dysfunction. Rathke cleft cysts are poorly described in the Polish literature. We aimed to characterize presenting symptoms, associated endocrine dysfunction, and concomitant disorders in the Polish population of patients with RCC. MATERIAL AND METHODS: We performed a retrospective analysis of medical records of 102 patients diagnosed with RCC between 2006 and 2021 at Heliodor Swiecicki Clinical Hospital in Poznan and Independent Public Clinical Hospital No. 4 in Lublin. RESULTS: The cohort was 72% female, with a mean age of 43 years. The median maximal cyst diameter was 7 mm. The majority of subjects were overweight or obese and presented lipid profile or glucose disturbances. Common presenting symptoms included headache, vertigo, and visual impairment. Less frequently we observed sexual dysfunction, irregular menses, galactorrhoea, or fatigue. Hormonal abnormalities were identified in 30% of patients, with hyperprolactinaemia being the commonest endocrinopathy (23%). Pituitary function in patients with RCC did not correlate with cyst size. Both concomitant pituitary adenomas and pineal cysts were diagnosed in 3% of patients. A considerable proportion of subjects were diagnosed with Hashimoto's thyroiditis and multinodular goitre. CONCLUSIONS: RCCs occur mostly in females and may result in a variety of symptoms and hormonal dysfunction. Patients require a full clinical and endocrine evaluation regardless of the cyst diameter. We report a substantial co-occurrence of RCC and metabolic disorders and primary thyroid diseases, which requires further investigation.

A cannulated prolactin series reduces the need for further investigations in women with infertility and lowers the number of false positive screening prolactin measurements.

BACKGROUND: The prevalence of hyperprolactinaemia in women presenting for infertility investigation has been found to be up to 17%, and many of these women are asymptomatic. Prolactin levels may be elevated by stress, including phlebotomy and not be of clinical significance. A cannulated prolactin study may be a useful way to discriminate this. AIM: To determine the utility of a cannulated prolactin series in women presenting with infertility who have a raised prolactin measurement at referral for first fertility consultation. MATERIALS AND METHODS: All women referred to two fertility centres had a prolactin level measured prior to first appointment over a two-year period. If the level remained elevated on the second measure after macroprolactin precipitation, women were referred for a cannulated prolactin series. If the prolactin concentration fell within the reference range during the series then the result was regarded as normal. RESULTS: Forty-four (2.7%) of 1660 women seen for a first specialist appointment had persistently raised prolactin concentrations after two samples and were referred for a cannulated series. The proportion of women whose prolactin was found to be normal during the cannulated prolactin series was 61% (95% CI 47-74%). Even in patients with a referral prolactin of greater than 1000 mU/L, 45% had a normal two-hour cannulated series. CONCLUSION: A high proportion (61%) of women with raised prolactin at time of referral for first specialist appointment had a normal prolactin after a two-hour cannulated series. A cannulated prolactin study can avoid unnecessary further investigations in these women.

Adverse body composition and lipid parameters in patients with prolactinoma: a case-control study.

BACKGROUND: Hyperprolactinaemia might cause adverse metabolic effects. The aim of our study was to compare parameters of body composition, glucose and lipid metabolism between untreated patients with prolactinoma and controls and to assess changes after initiation of cabergoline. METHODS: Case-control study with a retrospectively analyzed follow-up in patients with prolactinoma after initiation of cabergoline therapy. RESULTS: 21 patients with prolactinoma (9 micro- and 12 macroprolactinomas; 7 females) and 30 controls were analyzed. Patients with prolactinoma had significantly higher BMI than controls; fat mass did not differ between groups. Only men - but not women - with prolactinoma had significantly higher fat mass at all six sites measured compared to controls. Levels of LDL (130 (107-147.5) vs. 94.5 (80-127.5) mg/dl, p < 0.001) were significantly higher, levels of HDL (56 ± 16.7 vs. 69.2 ± 14.6 mg/dl, p = 0.004) significantly lower than in controls. Fasting glucose, HOMA-IR, HbA1c, adiponectin, CRP, and homocysteine did not differ between groups. After a median of 10 weeks (IQR 7-18 weeks) after initiation of cabergoline, total (from 212.5 ± 36.2 to 196.9 ± 40.6 mg/dl, p = 0.018) and LDL cholesterol (130 (107-147.5) to 106.5 (94.3-148) mg/dl, p = 0.018) had significantly decreased. Analyzing men and women separately, this change occurred in men only. CONCLUSIONS: Reasons for the association between prolactin and metabolic parameters include direct effects of prolactin on adipose tissue, hyperprolactinaemia-triggered hypogonadism and dopamine-agonist therapy per se. Altered lipid metabolism in patients with prolactinoma might imply an increased cardiovascular risk, highlighting the necessity to monitor metabolic parameters in these patients.

Circulating macroprolactin exhibits molecular heterogeneity and is not exclusively an antibody complex.

BACKGROUND: Macroprolactin (macPRL) is considered to be solely a prolactin antibody complex. We examined macPRL heterogeneity in samples from thirteen patients suspected of macroprolactinemia. METHODS: Polyethylene glycol (PEG) precipitation, gel permeation (GPC), protein-G affinity, and Lectin affinity chromatography were used to investigate the nature of macPRL. RESULTS: Using PEG, 8, 3, and 2 samples were macPRL positive, negative, and indeterminate respectively. Using GPC, prolactin appeared at high (H) (≥150 kDa), mid (M) (≥30 < 150 kDa), and low (L) (<30 k Da) forms. For macPRL positive samples, 52.3 to 95.0%, 3.6 to 34.1%, and 1.4 to 34.5% appeared at the (H), (M), and (L) regions respectively, compared with samples negative for macPRL with 1.2 to 5.1%, 60.0 to 79.4%, and 15.4 to 38.9% prolactin activity respectively. macPRL positive samples showed 30.4 to 86.5% binding to protein G column compared with negative samples at 1.2 to 5.1%. GPC-separated forms showed macPRL is heterogenous being either antibody bound (protein G studies) or glycosylated aggregates (lectin studies). Samples with identified macPRL forms were analysed using 4 immunoassay analysers. CONCLUSIONS: Samples with (H) and (M) macPRL forms showed significant positive bias in 2 immunoassays. The study is limited by the small number of samples and a larger scale study is required.

[Prolactinoma causing erectile dysfunction]. / Prolactinoma como causa de disfunción eréctil.

INTRODUCTION: Hyperprolactinaemia is an unusual cause of erectile dysfunction, yet erectile dysfunction is a common complaint in patients with hyperprolactinaemia. We present a patient with erectile dysfunction without symptoms suggesting hyperprolactinaemia. MATERIALS AND METHODS: Patient consulted with erectile dysfunction for the past 10 years. Decreased time and quality of erection with an IIEF score of 14/30. Lab reports: prolactin 90.2 ng/ml, FSH 1.6 mlU/ml, LH 1.8 UI/L, total testosterone .491 ng/ml. Brain MRI: lateral pituitary micro adenoma, 5mm in diameter. RESULTS: Patient in treatment with cabergoline 1mg per week, after treatment noticed improvement in erectile dysfunction and sexual desire. Actual prolactin 15.4 ng/ml. CONCLUSIONS: Up to 5% of patients with erectile dysfunction are diagnosed with a pituitary adenoma. Erectile dysfunction caused by pituitary neoplasms is a multifactorial disease and elevated prolactin has consequences on testosterone, LH, FSH, and dopamine precursor levels.

Monitoring patients receiving dopamine agonist therapy for hyperprolactinaemia.

The surveillance strategy for patients taking low dose cabergoline for hyperprolactinaemia is controversial. As more evidence has emerged that the risks of cardiac valvulopathy in this population of patients are low, fewer and fewer endocrinologists adhere strictly to the original medicines and healthcare products agency MHRA guidance of "at least" annual echocardiography. Strict adherence to this guidance would be costly in monetary terms (£5.76 million/year in the UK) and also in resource use (90,000 extra echocardiograms/year). This article reviews the proposed pathophysiological mechanism underlying the phenomenon of dopamine agonist valvulopathy, the characteristic echocardiographic changes seen, summarises the published literature on the incidence of valvulopathy with low dose cabergoline and examines the previous and current evidence-based screening guidelines.

Prolactin ordering patterns in psychiatric inpatients and the impact this has on patient management.

OBJECTIVE: Guidelines stipulate that baseline prolactin be ordered prior to commencing antipsychotic treatment to facilitate investigation of any subsequent hyperprolactinaemic symptoms. The aim was to observe when and why prolactin levels are ordered for psychiatry inpatients commencing or continuing antipsychotics and how this alters clinical management. METHODS: Psychiatry inpatients admitted to the Alfred Hospital, Melbourne, Australia, in 2018 with the diagnoses of psychosis, schizophrenia, schizo-affective disorder or bipolar affective disorder were retrospectively analysed. Results and clinical history data were collected in patients in whom prolactin was ordered during or within 12 months of the relevant admission. RESULTS: Of 592 patients admitted during this period, 90 had prolactin ordered. Eight (8.9%) of the 90 tests were for hyperprolactinaemic symptoms, while the remainder were routine blood work. The results altered clinical management in 10 of the 90 (11.1%) patients. Of these 10, 8 were symptomatic. In the six patients with first episode psychosis, only one had prolactin ordered prior to antipsychotic commencement. CONCLUSIONS: Adherence to guideline recommendations of baseline prolactin testing was poor. When established on antipsychotics, measuring prolactin rarely changed management in asymptomatic patients; however, it did in those with hyperprolactinaemic symptoms. Measuring prolactin in asymptomatic patients on antipsychotics appears unhelpful.