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Low prolactin levels have been found to impair libido and arousal, as well as to reduce wellbeing in young women.The aim of this study was to investigate whether drug-induced hypoprolactinaemia affects male sexual function and depressive symptoms.The study population consisted of three groups of young and middle-aged men. Two groups were treated with dopamine agonists because of previous hyperprolactinaemia but differed in current prolactin levels, which were3ng/ml (n=12; group 1) or within the reference range (3-20ng/ml) (n=20; group 2). The control group (group 3) included 24 dopamine agonist-naïve normoprolactinaemic men. During the study, doses of dopaminergic agents in group 1 were reduced by 25-50% compared to doses before the start of the study. Circulating levels of prolactin, testosterone, free calculated testosterone, dehydroepiandrosterone-sulphate, oestradiol and gonadotropins were measured upon enrolment in the study and six months later. Moreover, at the beginning and the end of the study, all men enrolled completed questionnaires assessing sexual functioning (IIEF-15) and depressive symptoms (BDI-II).Group 1 differed from groups 2 and 3 in domain scores for sexual desire and erectile function, and in the overall BDI-II score. It was also characterised by lower levels of total testosterone and calculated free testosterone. Reduction of drug doses normalised sexual desire and erectile function, reduced BDI-II scores and increased prolactin as well as total and free calculated testosterone. Groups 2 and 3 did not differ from each other in sexual functioning, depressive symptoms or hormone levels.The results obtained indicate that men with dopamine agonist-induced hypoprolactinaemia are characterised by impaired sexual functioning and reduced wellbeing. These disturbances are a consequence of subnormal prolactin levels and do not seem to reflect adverse effects of dopamine agonists.

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.

Background: Prolactin has multiple biological functions and hyperprolactinaemia is a common condition in clinical practice in both females and males. It has many etiologies and may present with variable symptoms to health care workers. Aims and Objectives: To study the various etiologies and clinical presentation of patients presenting with hyperprolactinaemia in a tertiary care medical college and hospital in West Bengal to aid in quick decision management. Materials and Methods: The current study was a cross-sectional study with follow up conducted over a period of one year in the Department of Gynecology and Obstetrics, Jagannath Gupta Institute of Medical College and Hospital. Following sample size calculation, a total of 1824 women were enrolled for the study of which 53 were found to have raised prolactin level (after following proper inclusion and exclusion criteria) They were subsequently further examined and followed up. Results: Majority of the subjects studied belonged to 20-29 age group (49.05%) followed by 30-39 years age group (35.85%). The most common cause of hyperprolactinaemia in our study were idiopathic (24.53%) followed by drugs (22.64%) and pituitary adenoma. Most of the patients with hyperprolactinaemia, presented with complain of infertility (56.6%), menstrual abnormality (50.94%) and galactorrhoea (18.87%) in our study. Therapeutic drugs used for various reasons were one of the main cause of hyperprolactinaemia (22.64%) and mainly due to use of proton pump inhibitor with prokinetics use. Conclusion: Hyperprolactinaemia is very much common in patients with infertility, menstrual abnormality or galactorrhoea and mostly are due to idiopathic or drug induced causes. With early initiation of treatment most of the causes and effects can be cured.

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.

What is known and objective Metformin was found to normalize secretory function of overactive pituitary cells. Its effect on circulating thyrotropin levels was more pronounced in women receiving exogenous vitamin D. The aim of the current study was to investigate whether vitamin D status determines the impact of metformin on prolactin levels in premenopausal women with hyperprolactinaemia. Methods The study population consisted of three groups of women with prediabetes and elevated prolactin levels: vitamin D-naive women with vitamin D insufficiency (group 1; n = 19), women receiving vitamin D preparations because of vitamin D deficiency (group 2 n = 20), as well as vitamin D-naive women with normal vitamin D status (group 3 n = 23). All participants were then treated with metformin (2.55-3 g daily). Circulating levels of glucose, insulin, prolactin, thyrotropin, free thyroid hormones, gonadotropins, estradiol, calcium and 25-hydroxyvitamin were determined at baseline and six months later. Results and discussion At baseline, prolactin levels were higher in group 1 than in the remaining groups of patients. Although metformin decreased glucose levels and improved insulin sensitivity in all treatment groups, this effect was more pronounced in groups 2 and 3. Only in subjects with 25-hydroxyvitamin D levels within the reference range, metformin reduced prolactin levels. The impact on prolactin levels correlated with 25-hydroxyvitamin D levels and with the improvement in insulin sensitivity. The drug produced a neutral effect on circulating levels of thyrotropin, free thyroid hormones, gonadotropins, estradiol, calcium and 25-hydroxyvitamin D. What is new and the conclusion The results of the current study suggest that the impact of metformin on secretory function of overactive lactotropes depends on the vitamin D status of patients.

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.

Lactatio sine graviditate of the bitch can become clinically relevant in particularly severe manifestations. The aim of the study was to relate the hormone pattern consisting of progesterone (P4), estradiol 17β (E2) and prolactin to the time of occurrence of lactatio sine graviditate in the course of metoestrus and anoestrus as well as to its symptomatology.Sixty-eight bitches with apparent lactatio sine graviditate were divided into 3 groups according to their cycle status. All bitches were examined for gynaecological findings. Furhtermore, their blood progesterone, oestrogen, and prolactin concentrations were determined and compared with the 133-day hormone profile of 7 control animals.Lactatio sine graviditate occurring in early metoestrus was characterised more by a shifted P4:E2 ratio than by hyperprolactinaemia. Overall, the prolactin concentration in the peripheral blood was significantly increased. Analysis of the individual cases revealed that hyperprolactinaemia was present to varying degrees. It could be detected in almost all bitches that showed full symptomatology at the end of metoestrus or at the beginning of anoestrus. Only then clinical signs correlated with an increased prolactin concentration in the peripheral blood. In most cases, the estradiol-17β concentration was within the reference range.The study indicates that the administration of prolactin inhibitors alone is not indicated in all cases of lactatio sine graviditate and that the timepoint of onset of the clinically relevant symptoms and the current prolactin level should be taken into account in the treatment of affected bitches.Die Lactatio sine graviditate der Hündin kann in besonders starker Ausprägung klinische Relevanz erlangen. Ziel der Studie war, das Hormonmuster, bestehend aus Progesteron (P4), Östradiol 17β (E2) und Prolaktin, in Beziehung zum Zeitpunkt des Auftretens einer Lactatio sine graviditate im Verlauf des Met- und Anöstrus sowie zu deren Symptomatik zu setzen.Achtundsechzig Hündinnen mit klinischer Lactatio sine graviditate wurden entsprechend ihrem Zyklusstatus in 3 Gruppen eingeteilt. Bei jeder Hündin erfolgten eine eingehende gynäkologische Untersuchung sowie eine Bestimmung der Progesteron-, Östrogen- und Prolaktin-Konzentrationen im Blut. Die Hormonkonzentrationen der Probanden wurden mit dem 133-Tage-Hormonprofil von 7 Kontrolltieren verglichen.Eine im frühen Metöstrus auftretende Lactatio sine graviditate war mehr von einem verschobenen P4:E2-Verhältnis geprägt als von einer Hyperprolaktinämie. Insgesamt betrachtet war der Prolaktingehalt im peripheren Blut signifikant erhöht. Bei der Analyse der Einzelfälle fiel auf, dass eine Hyperprolaktinämie in unterschiedlicher Ausprägung vorlag. Bei nahezu allen Hündinnen, die die volle Symptomatik am Ende des Metöstrus, zu Beginn des Anöstrus aufwiesen, ließ sich eine Hyperprolaktinämie feststellen. Nur dann korrelierten die klinischen Zeichen mit einer erhöhten Prolaktinkonzentration im peripheren Blut. In den meisten Fällen lag die Östradiol-17β-Konzentration im Referenzbereich.Relevanz Die Untersuchung gibt einen Hinweis darauf, dass eine alleinige Antiprolaktingabe nicht in allen Fällen einer Lactation sine graviditate angezeigt ist, sondern der Zeitpunkt des Auftretens der klinisch relevanten Symptome und der aktuelle Prolaktinwert im Therapiekonzept Berücksichtigung finden sollten.

Psychotropic medication treatment can cause elevated serum prolactin levels and hyperprolactinaemia (HPRL). Reports have suggested that aripiprazole may decrease elevated prolactin. The aim of this review was to assess evidence for the efficacy of adjunct aripiprazole in the treatment of psychotropic-induced HPRL. PubMed and Google Scholar were searched to identify randomised placebo-controlled trials (RCTs) of adjunct aripiprazole in patients with HPRL attributed to primary psychotropic medications. Data for individual patients from case studies, chart reviews and open-label studies were also identified and assessed. Six RCTs, with a total of 609 patients, met inclusion criteria. Primary psychotropics included risperidone, haloperidol, paliperidone, fluphenazine and loxapine. Reductions in prolactin from baseline, before the introduction of aripiprazole, were significantly greater for adjunct aripiprazole than for adjunct placebo in all the studies (p = 0.04 to p

Nonfunctionning pituitary macroadenomas (NFPMA) are benign tumors that cause symptoms of mass effects including hypopituitarism. Their primary treatment is transsphenoidal surgery. We aimed to determine the outcome of pituitary hormone deficits after surgical treatment of NFPMA and to identify factors predicting hormonal recovery. We retrospectively included 246 patients with NFPMA diagnosed and operated in one of the two participating centers. All hormonal axes were evaluated except growth hormone (GH). Postoperative improvement of pituitary endocrine function was considered if at least one hormonal deficit had recovered and a lower total number of deficits was observed 1 year after surgery. 80% (n = 197) of patients had one or more pituitary deficits and 28% had complete anterior hypopituitarism. Besides GH, the gonadotropic and thyrotropic axes were the most commonly affected (68% and 62%, respectively). The number of hypopituitary patients dropped significantly to 61% at 1 year (p

Introduction Hyperprolactinemia may be due to physiological or pathological causes, and may be asymptomatic or induce hypogonadism, infertility, and/or galactorrhea. It is important to take prolactin samples while avoiding stress, as this may increase prolactin levels. Therefore, our aim was to assess the value of prolactin serial sampling after brachial vein cannulation. Patients and methods Sixty-six patients (34.9 ± 11.8 years of age, 92.4% female) with an initial elevated random prolactin level were included. A prolactin sample was drawn at baseline and after a 30 min rest. Results The median referral prolactin level was 37.4 ng/ml (interquartile range [IQR* 23.3), the baseline prolactin level at serial sampling was 19.5 ng/ml (IQR 8), and the value after a 30 min rest was 17.1 ng/ml (IQR 7.9). Hyperprolactinemia was not confirmed by serial sampling in 45 patients (68.2%). There were no statistically significant differences in referral prolactin levels between patients with and without confirmed hyperprolactinemia (41.2 ng/ml and 36.7 ng/ml respectively, p = 0.3). Galactorrhea was found in 13.6% of patients, amenorrhea or oligomenorrhea in 28.8%, infertility in 7.6%, erectile dysfunction in 4.6%, and gynecomastia in 3%, while 45.5% were asymptomatic. There were no statistical differences regarding the presence or absence of any of these symptoms and subsequent confirmed hyperprolactinemia. Fifty-seven patients (86.4%) were discharged after the results of the prolactin serial sampling were obtained. Conclusions Prolactin serial sampling may be a useful test to detect artefactual hyperprolactinemias, thus avoiding unnecessary additional tests and treatments.

Purpose\ud Moderate hyperprolactinaemia (2–5 times upper limit of normal) occurring in a patient with a normal pituitary MRI is generally considered to be due to a lesion below the level of detection of the MRI scanner assuming macroprolactin and stress have been excluded. Most patients with mild-to-moderate hyperprolactinaemia and a normal MRI respond to dopamine agonist therapy. We present the rare case of a patient who had prolactin elevation typical of a prolactin-secreting pituitary macroadenoma,with a normal cranial MRI, and in whom the prolactin rose further with dopamine agonist treatment. Subsequent investigations revealed ectopic hyperprolactinaemia to a uterine tumor resembling ovarian sex cord tumor (UTROSCT) which resolved following tumor resection. Although mostly considered to be benign, the UTROSCT recurred with recurrent hyperprolactinaemia and intraabdominal metastases.\ud \ud Methods\ud We have systematically and critically reviewed existing literature relating to ectopic hyperprolactinaemia in general and UTROCST specifically.\ud \ud Results\ud Fewer than 80 cases of UTROSCTs have been reported globally of which about 23% have shown malignant behaviour. There are fewer than 10 cases of paraneoplastic hyperprolactinaemia originating from uterine neoplasms including one other case of ectopic hyperprolactinaemia to a UTROSCT.\ud \ud Conclusions\ud Our case demonstrates the importance of screening for extracranial hyperprolactinaemia in the context of: (1) substantially raised prolactin (10× ULN) and (2) normal cranial MRI assuming macroprolactin has been excluded. The majority of extracranial ectopic prolactin-secreting tumors occur in the reproductive organs.Methods: We have systematically and critically reviewed existing literature relating to ectopic hyperprolactinaemia in general and UTROCST specifically. \ud Results: Fewer than 80 cases of UTROSCTs have been reported globally of which about 23% have shown malignant behaviour. There are fewer than 10 cases of paraneoplastic hyperprolactinaemia originating from uterine neoplasms including one other case of ectopic hyperprolactinaemia to a UTROSCT. \ud Conclusions: Our case demonstrates the importance of screening for extracranial hyperprolactinaemia in the context of: (1) substantially raised prolactin (10xULN) and (2) normal cranial MRI assuming macroprolactin has been excluded. The majority of extracranial ectopic prolactin-secreting tumors occur in the reproductive organs.

Summary Lymphocytic hypophysitis is a rare neuroendocrine disease characterised by an autoimmune inflammatory disorder of the pituitary gland. We report a 50-year-old woman who presented with headaches and bilateral sixth cranial nerve palsies. MRI of the pituitary revealed extensive fibrosis involving the sellar and extending into both cavernous sinuses causing bilateral occlusion of the internal carotid arteries (ICA). Transphenoidal biopsy confirmed the diagnosis of infiltrative fibrotic lymphocytic hypophysitis. Symptoms resolved with high dose of oral steroids but relapsed on tapering, requiring several treatments of i.v. pulse steroids over 8 months. Rituximab combined with mycophenolate mofetil was required to achieve long-term symptom relief. Serial MRI pituitary imaging showed stabilisation of her disease without reduction in sellar mass or regression of ICA occlusion. The patient’s brain remained perfused solely by her posterior circulation. This case demonstrates an unusual presentation of a rare disease and highlights a successful steroid-sparing regimen in a refractory setting. Learning points: Lymphocytic hypophysitis is a rare inflammatory disorder of the pituitary gland. In exceptional cases, there is infiltration of the cavernous sinus with subsequent occlusion of the internal carotid arteries. First-line treatment of lymphocytic hypophysitis is high-dose glucocorticoids. Relapse after tapering or discontinuation is common and its use is limited by long-term adverse effects. There is a paucity of data for treatment of refractory lymphocytic hypophysitis. Goals of treatment should include improvement in symptoms, correction of hormonal insufficiencies, reduction in lesion size and prevention of recurrence. Steroid-sparing immunosuppressive drugs such as rituximab and mycophenolate mofetil have been successful in case reports. This therapeutic combination represents a viable alternative treatment for refractory disease.

SUMMARYAdvocating for good physical healthcare for their patients is of the utmost importance to psychiatrists. This narrative review focuses on one part of this large goal, the topic of hyperprolactinaemia from the perspective of mental healthcare. For psychiatrists this often includes managing raised prolactin levels in the context of medication. However, they must consider the wider differentials of a raised prolactin level and the possible impact of treatments. For that reason, in this review we start with an overview of prolactin physiology before considering hyperprolactinaemia both in the context of antipsychotic therapy and its wider differentials, including prolactinoma. Investigation and management are considered and key practice points developed.

Hyperprolactinemia is a known adverse drug reaction to antipsychotic treatment. Antipsychotic blood levels are influenced by cytochrome P450 enzymes, primarily CYP2D6. Variation in CYP450 genes may affect the risk of antipsychotic-induced hyperprolactinemia. We undertook a systematic review and meta-analysis to assess whether CYP2D6 functional genetic variants are associated with antipsychotic-induced hyperprolactinemia. The systematic review identified 16 relevant papers, seven of which were suitable for the meta-analysis (n = 303 participants including 134 extreme metabolisers). Participants were classified into four phenotype groups as poor, intermediate, extensive, and ultra-rapid metabolisers. A random effects meta-analysis was used and Cohen's d calculated as the effect size for each primary study. We found no significant differences in prolactin levels between CYP2D6 metabolic groups. Current evidence does not support using CYP2D6 genotyping to reduce risk of antipsychotic-induced hyperprolactinemia. However, statistical power is limited. Future studies with larger samples and including a range of prolactin-elevating drugs are needed.

The use of opioids is becoming a global epidemic, leading to a rise in the occurrence and recognition of the effects of opioid drugs on the endocrine system. Nonetheless, opioid-induced endocrinopathies still remain underdiagnosed, mainly because of symptom under-reporting by patients and poor clinician awareness. Hypogonadism is the most well recognised consequence of opioid use, but the inhibitory effects of opioid drugs on the hypothalamo-pituitary-adrenal axis and their negative effects on bone health also require attention. Hyperprolactinaemia might be detected in opioid users, but clinically relevant thyroid dysfunction has not been identified. The effects of opioids on other hormones have not been clearly defined. Assessment of gonadal and adrenal function (particularly if high index of clinical suspicion of hypogonadism or hypoadrenalism) and evaluation of bone health are advised in people that use opiods. Discontinuation or reduction of opioid dose and appropriate hormone replacement are the management approaches that should be considered for hypogonadism and hypoadrenalism. Further research is needed to facilitate the development of evidence-based guidelines on the diagnosis and optimal management of opioid-induced endocrinopathies.

Introduction Screening of polycystic ovary syndrome (PCOS) women for hypothyroidism and hyperprolactinemia was suggested, because the undiagnosed hypothyroidism and hyperprolactinemia can aggravate the PCOS symptoms. Aim of the study To determine whether the insulin resistance (IR), hypothyroidism, and hyperprolactinemia are common endocrine disorders associated with the PCOS. Material and methods One hundred and twenty PCOS women were compared to 120 non-PCOS controls in this study. Participants’ day 2-3 hormonal profile and insulin resistance (IR) using the fasting glucose and fasting insulin were evaluated. Collected data were analyzed to determine whether the IR, hypothyroidism, and hyperprolactinemia are common endocrine disorders associated with the PCOS. Results TSH and prolactin were significantly high in PCOS women (6.4 ±4.2 and 934 ±102.3, respectively) than controls (3.5 ±3.3 and 445 ±77.5 mIU/ml, respectively) (p = 0.004 and 0.001, respectively). The PCOS women had significantly high relative risk of IR (RR 3.0 (95% CI: 1.9-4.7) p < 0.0001), hypothyroidism (RR 3.4; 95% CI: 1.7-6.9) (p = 0.0005), and hyperprolactinaemia (RR 3.15; 95% CI: 1.8-5.6) (p = 0.0001) than controls. The PCOS women had higher odds of IR (OR 4.8; 95% CI: 2.6-8.8) (p < 0.0001), hypothyroidism (OR 4.29; 95% CI: 1.9-9.4) (p = 0.0003), and hyperprolactinaemia (OR 4.27; 95% CI: 2.1-8.5) (p < 0.0001) than controls. Conclusions TSH and prolactin were significantly high in studied PCOS women, and 47.5% of the studied PCOS women had IR. The PCOS women had significantly higher odds and relative risks of IR, hypothyroidism, and hyperprolactinemia than controls. IR, hypothyroidism, and hyperprolactinemia are common endocrine disorders associated with PCOS.

Osteochondromas are common in the long bones and relatively rare in the head and neck regions. We herein report a case of a solitary temporal bone osteochondroma associated with a functional pituitary adenoma hypersecreting prolactin. The patient was a 48-year-old man with progressive, painless temporal swelling associated with gradual visual loss, gynaecomastia, erectile dysfunction, and loss of libido. A brain computed tomography scan with bone windows showed right temporal sessile bony expansion and a pituitary tumour. A pituitary function test revealed hyperprolactinaemia. His symptoms resolved with medical management, and excisional biopsy of the temporal tumour confirmed an osteochondroma. To the best of our knowledge, this is the first reported case of a solitary temporal bone osteochondroma with a functional pituitary adenoma hypersecreting prolactin.

Background First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal remission rates are approximately 34%. Therefore, many patients require prolonged DA treatment, while side effects negatively impact health-related quality of life (HRQoL). Endoscopic transsphenoidal resection is reserved for patients with severe side effects, or with DA-resistant prolactinoma. Surgery has a good safety profile and high probability of remission and may thus deserve a more prominent place in prolactinoma treatment. The hypothesis for this study is that early or upfront surgical resection is superior to DA treatment both in terms of HRQoL and remission rate in patients with a non-invasive prolactinoma of limited size. Methods We present a combined randomised clinical trial and observational cohort study design, which comprises three unblinded randomised controlled trials (RCTs; PRolaCT-1, PRolaCT-2, PRolaCT-3), and an observational study arm (PRolaCT-O) that compare neurosurgical counselling, and potential subsequent endoscopic transsphenoidal adenoma resection, with current standard care. Patients with a non-invasive prolactinoma (< 25 mm) will be eligible for one of three RCTs based on the duration of pre-treatment with DAs: PRolaCT-1: newly diagnosed, treatment-naïve patients; PRolaCT-2: patients with limited duration of DA treatment (4–6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for > 2 years. PRolaCT-O will include patients who decline randomisation, due to e.g. a clear treatment preference. Primary outcomes are disease remission after 36 months and HRQoL after 12 months. Discussion Early or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three RCTs and an observational cohort study. Within the three RCTs, patients will be randomised between neurosurgical counselling and standard care. The observational study arm will recruit patients who refuse randomisation and have a pronounced treatment preference. PRolaCT will collect randomised and observational data, which may facilitate a more individually tailored practice of evidence-based medicine. Trial registration US National Library of Medicine registry (ClinicalTrials.gov) NCT04107480. Registered on 27 September 2019, registered retrospectively (by 2 months).

BackgroundAntipsychotic polypharmacy (APP) occurs commonly but it is unclear whether it is associated with an increased risk of adverse drug reactions. Electronic health records (EHRs) offer an opportunity to examine APP using real-world data. In this study, we use EHR data to identify periods when patients were prescribed 2+ antipsychotics and compare these with periods of antipsychotic monotherapy. To determine the relationship between APP and subsequent instances of adverse drug reactions: QT interval prolongation, hyperprolactinaemia, and increased body weight (body mass index [BMI] ≥ 25).MethodsWe extracted anonymised EHR data. Patients aged 16+ receiving antipsychotic medication at Camden & Islington NHS Foundation Trust between 1 January 2008 and 31 December 2018 were included. Multilevel mixed-effects logistic regression models were used to elucidate the relationship between APP and the subsequent presence of QT interval prolongation, hyperprolactinaemia, and/or increased BMI following a period of APP within 7, 30, or 180 days respectively.ResultsWe identified 35,409 observations of antipsychotic prescribing among 13,391 patients. APP was associated with a subsequent increased risk of hyperprolactinaemia (adjusted odds ratio 2.46; 95% C.I. 1.87-3.24) and of having a BMI > 25 (adjusted odds ratio 1.75; 95% C.I. 1.33-2.31) in the period following the APP prescribing.ConclusionsOur observations suggest that APP should be carefully managed with attention to hyperprolactinaemia and obesity.

There are significant differences between men and women in the efficacy and tolerability of antipsychotic drugs. Here, we provide a comprehensive overview of what is currently known about the pharmacokinetics and pharmacodynamics of antipsychotics in women with schizophrenia spectrum disorders (SSDs) and translate these insights into considerations for clinical practice. Slower drug absorption, metabolism and excretion in women all lead to higher plasma levels, which increase the risk for side-effects. Moreover, women reach higher dopamine receptor occupancy compared to men at similar serum levels, since oestrogens increase dopamine sensitivity. As current treatment guidelines are based on studies predominantly conducted in men, women are likely to be overmedicated by default. The risk of overmedicating generally increases when sex hormone levels are high (e.g. during ovulation and gestation), whereas higher doses may be required during low-hormonal phases (e.g. during menstruation and menopause). For premenopausal women, with the exceptions of quetiapine and lurasidone, doses of antipsychotics should be lower with largest adjustments required for olanzapine. Clinicians should be wary of side-effects that are particularly harmful in women, such as hyperprolactinaemia which can cause oestrogen deficiency and metabolic symptoms that may cause cardiovascular diseases. Given the protective effects of oestrogens on the course of SSD, oestrogen replacement therapy should be considered for postmenopausal patients, who are more vulnerable to side-effects and yet require higher dosages of most antipsychotics to reach similar efficacy. In conclusion, there is a need for tailored, female-specific prescription guidelines, which take into account adjustments required across different phases of life.

Hyperprolactinaemia is one of the commonest non-diabetes endocrine disorder seen by Endocrinologists. Prolactin is a polypeptide hormone secreted by the anterior pituitary gland. Its main physiological role is in milk production. Hyperprolactinaemia is more common among females and there is paucity of literature on hyperprolactinaemia among men. The causes of hyperprolactinaemia include physiological causes (such as sleep), drugs, sellar masses, including prolactinoma, other endocrine disorders such as hypothyroidism. The clinical presentation in males results from the disruption of the hypothalamus-pituitary-testicular axis and mass effect. It is an important and often overlooked cause of hypogonadism in males. Men usually present with macroprolactinomas with accompanying symptoms of mass effect such as visual impairment. Diagnosis of hyperprolactinaemia is made from relevant symptoms and signs and confirmed by immunoassay of the serum prolactin. Other relevant investigations need to be done to identify the potential causes of the disorder. Magnetic resonance imaging is the radiological investigation of choice to visualize the pituitary. Treatment of hyperprolactinaemia in males is dependent on aetiology and symptomatology. Some medications may need to be stopped or changed. Pharmacotherapy with dopamine agonists is the first line treatment of prolactinomas. Symptomatic cases of prolactinomas with drug resistance or drug intolerance are referred for surgery or radiotherapy

Key messages Evelyn, a 20-year-old student, attends her university general practitioner (GP) practice for the first time with a history of her periods becoming further apart and then stopping. Her periods had been regular previously, when living at home, but they have become more irregular in the last 12 months. Her body mass index (BMI) is 19 kg/m2 (weight 45 kg, height 1.53 m). Although definitions vary, secondary amenorrhoea should be suspected if a woman has not had a period for 3–6 months with previous regular periods or 6–12 months in a woman with preceding oligomenorrhoea. Secondary amenorrhoea has a prevalence of 3%–4% in women of reproductive age1 and can present a diagnostic challenge, with a wide range of underlying causes, often with minimal or subtle signs (figure 1). In the context of a normal puberty, the most common causes in this age group are pregnancy, hypothalamic dysfunction, polycystic ovary syndrome (PCOS), hyperprolactinaemia and drugs (including hormonal contraception and recreational drugs). Figure 1 Causes of secondary amenorrhoea. A detailed menstrual history, from menarche to the last menstrual period, is required to verify secondary amenorrhoea and elicit relevant timescales and any associated factors. A sexual and contraceptive history should then be used to assess pregnancy risk and exclude causes related to hormonal contraception. In this case, Evelyn reports “about ten” casual partners during her current university …

Gigantomastia is characterised by excessive breast growth and can occur as a rare, drug-induced adverse event. D-penicillamine is the most frequent cause of drug-induced gigantomastia. Only one case of gigantomastia due to bucillamine, an analogue of D-penicillamine, has been reported so far. We herein report a case of bucillamine-induced gigantomastia presenting with acute enlargement of the bilateral breasts and accessory breast tissue in the axillae 7 months after the start of bucillamine therapy. Awareness about this rare adverse event is important since bucillamine is still widely used in Japan and Korea.

Background:Natural killer cells (NKC) are a major component of the innate immune response to HCV, mediating their effects through TRAIL and IFN-γ. However, their function is diminished in chronic HCV patients (HCVp). Prolactin is an immunomodulatory hormone capable of activating NKC.Objective:The study aims to explore if hyperprolactinemia can activate NKC in HCVp.Methods:We treated twelve chronic HCVp (confidence level =95%, power =80%) for 15 days with Levosulpiride plus Cimetidine to induce mild hyperprolactinemia. Before and after treatment, we determined TRAIL and NKG2D expression on peripheral blood NKC, along with cytokine profiles, viral loads and liver function. We also evaluated in vitro effects of prolactin and/or IL-2 on NKC TRAIL or NKG2D expression and IFN-γ levels on cultured blood mononuclear cells from 8 HCVp and 7 healthy controls.Results:The treatment induced mild hyperprolactinemia and increased TRAIL expression on NKC as well as the secretion of IL-1ra, IL-2, PDGF and IFN-γ. Viral loads decreased in six HCVp. IL-2 and TRAIL together explained the viral load decrease. In vitro, prolactin plus IL-2 synergized to increase TRAIL and NKG2D expression on NKC from HCVp but not in controls.Conclusion:Levosulpiride/Cimetidine treatment induced mild hyperprolactinaemia that was associated with NKC activation and Th1-type cytokine profile. Also, an increase in TRAIL and IL-2 was associated with viral load decrease. This treatment could potentially be used to reactivate NKC in HCVp.

Metformin was found to reduce elevated prolactin levels in women but not in men. The current study was aimed at investigating whether endogenous testosterone determines the impact of metformin on lactotroph function in men. This prospective case-control study included 28 men with recently diagnosed type 2 diabetes mellitus and mild or moderate hyperprolactinaemia, 14 of whom had low testosterone levels, while in the remaining 14 ones' testosterone levels were within the reference range. All participants received metformin (2.55-3 g daily) for the following 4 months. Circulating levels of glucose, insulin, prolactin, testosterone, oestradiol, gonadotropins, sex hormone-binding globulin adrenocorticotropic hormone, insulin-like growth factor-1, thyrotropin and free thyroid hormones were measured at the beginning and at the end of the study. Although metformin reduced plasma glucose levels and improved insulin sensitivity in both groups, this effect was stronger in participants with low testosterone levels. Only in patients with abnormally low testosterone levels, the drug decreased prolactin levels. This effect, which was accompanied by an increase in luteinizing hormone levels, was inversely correlated with baseline testosterone and calculated free testosterone levels, and positively with treatment-induced improvement in insulin sensitivity. In both treatment groups, metformin produced a neutral effect on plasma levels of the remaining hormones. The obtained results suggest that endogenous testosterone may attenuate the impact of metformin on lactotropic cells.

Introduction: The predominance of high-molecular-weight forms of prolactin in plasma is referred to as macroprolactinaemia. Unlike monomeric hyperprolactinaemia, no previous study has investigated cardiometabolic risk factors in subjects with elevated macroprolactin content. Material and methods: We studied two age-, weight-, and blood pressure-matched groups of premenopausal women: 11 women with macroprolactinaemia and 11 women with prolactin levels within the reference range. The outcomes of interest included: glucose homeostasis markers, plasma lipids, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D. Results: Circulating levels of hsCRP and 2-h postchallenge plasma glucose, as well as the homeostatic model assessment 1 of insulin resistance ratio, were higher, while levels of HDL cholesterol and 25-hydroxyvitamin D were lower in women with macroprolactinaemia than in women without elevated levels of prolactin. In women with elevated levels of big-big prolactin, values of hsCRP and 25-hydroxyvitamin D correlated with the degree of insulin resistance and, similarly to HDL cholesterol and 2-h postchallenge plasma glucose, with macroprolactin content. There were no differences between the study groups in concentrations of fasting glucose, total cholesterol, LDL cholesterol, triglycerides, uric acid, fibrinogen, and homocysteine. Conclusions: The obtained results indicate that young women with macroprolactinaemia seem to be characterised by slightly increased cardiometabolic risk.

Prolactin as a hormone secreted by lactotrophs of the adenocyphosis primarily affects lactation in mammals, that is, on the production of milk (lactogenesis), the development and branching of the milk channels (mamogenesis) and the removal of milk through the nipples (galactopoezis). Other significant biological effects of prolactin include maintaining the internal homeostasis of the organism acting as an osmoregulatory hormone, as an luteotrophic hormone and has an immunological role in the body. Excretion of prolactin is regulated by the action of prolactin stimulating and prolactin inhibiting factors of the hypothalamus. By maintaining a balance in the excretion of these factors, the level of concentration of prolactin in the serum is in normal reference values. Disturbance in the excretion of dopamine as the strongest prolactin secretion inhibitor increases the level of prolactin, a condition known as hyperprolactinaemia, in which all hormones important for the normal menstrual cycle are inhibited, leading to reduced production of ovarian follicles and ovarian steroids, anovulation and sterility in women. The purpose of this study was to determine the level of prolactin in a group of patients with established hyperprolactinaemia in relation to the control group of patients and determining the level of gonadotrophic hormones FSH and LH in hyperprolactinemic patients in relation to the control group. The aim was also to see the effect of Bromergon or Dostinex in hyperprolactinemic patients on the level of FSH and LH after receiving the therapy. Patients aged 25 to 35 years with pre-diagnosed hyperprolactinaemia were examined. Prolactin, FSH and LH were examined from the parameters. Patients were divided into three groups, a control group of patients, a group of patients with diagnosed hyperprolactinaemia, and a group of patients treated with Bromergon or Dostinex. From the results obtained, it became clear that in the control group of patients, the levels of prolactin, FSH and LH were in normal reference values. In the hyperprolactinemic patients, prolactin has been significantly increased, but after the dose of Dostinex or Bromergon in the treated group, the level of prolactin significantly decreases to values close to the control group. It was noted that the concentration of FSH in hyperprolactinemic patients was lower in relation to the concentration of FSH in the control group, and the serum FSH level in patients treated with antiprolactin therapy was increased to a level higher than the concentration of FSH in the control group.The level of LH in the serum from hyperprolactinemic patients is less than LH level in the control group, but to a lesser extent compared to the level of FSH under the same conditions. In the treatment of patients with antiprolactin therapy there is an increase in serum concentrations of LH with values significantly higher than the control group.

Te article provides an overview of foreign and domestic literature on the development of complications associated with neuroleptic hyperprolactinaemia in patients with schizophrenia in the course of prolonged antiretroviral therapy with antipsychotics. Most researchers agree that long-term neuroleptic hyperprolactinemia signifcantly impairs the physical health of patients with mental disorders. Timely diagnosis and correction of this side effect of psychopharmacotherapy will signifcantly reduce the risk of complications and improve the social functioning of patients with schizophrenic disorders.

Ectopic prolactin production from a malignancy is infrequently reported. We report here a 60-year-old gentleman who presented with hyperprolactinaemia (9100 mIU/L) causing expressible galactorrhoea, decreased libido and fatigue thought to be due to ectopic prolactin secretion from a metastatic melanoma. Upon initiation of pembrolizumab, the patient's symptoms resolved and he became normoprolactinaemic. This corresponded with a partial response on radiological imaging. Although the core biopsy of the metastatic melanoma did not exhibit immunostaining for prolactin, we believe that only a subset of the tumour cells possesses prolactin-secreting capacity. This case illustrates the need to consider ectopic prolactin production for a solid malignant tumour as a rare cause of hyperprolactinaemia in patients with a normal pituitary MRI, in the absence of other causes.

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 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.

Background Pituitary lesions are present in >10% of the population. Approximately one in 1000 people has a symptomatic pituitary tumour, which may cause clinical problems from mass effect, hormonal hypersecretion and impairment of normal pituitary function. Objective The aim of this article is to outline the potential causes of a sellar and parasellar mass, with an emphasis on the presenting clinical features and screening investigations that are applicable to doctors working in the primary care setting. Discussion There is a broad range of causes of a sellar/parasellar mass. Pituitary adenomas and Rathke's cleft cysts are the most frequently encountered. Prolactinomas are the most common functioning tumour and tend to present as macroadenomas in men, while hyperprolactinaemia is associated with 15% of secondary amenorrhoea in women. Acromegaly and Cushing's disease are rare but important diagnoses to detect. Pituitary disease is optimally managed in a specialist centre in the context of an established multidisciplinary team.

Duloxetine is a serotonin-noradrenaline reuptake inhibitor (SNRI). The noradrenergic effects contribute to the treatment of painful physical symptoms. Hyperprolactinaemia and galactorrhea are recognized side effects of psychotropic drugs used in the treatment of psychiatric diseases. Although hyperprolactinaemia is a known side effect of the tricyclic antidepressants, evidence on hyperprolactinaemia and galactorrhoea induced by the selective serotonin reuptake inhibitors (SSRIs) and the SNRIs is limited. Hyperprolactinaemia due to SSRI or SNRI therapy is usually asymptomatic and is diagnosed after a detailed examination of the patient following the emergence of galactorrhea. In this report, a case who developed amenorrhea, galactorrhea, and hyper-prolactinaemia identified at the 5th month of duloxetine for major depression will be discussed. After a month of drug-free period and cabergoline treatment, the prolactin levels returned to normal.

Prolactin-secreting leiomyomas are rare, with only eight cases reported in the literature. This case describes a 37-year-old female with hyperprolactinaemia (1846 mIU/L; 85–500 mIU/L) refractory to cabergoline causing infertility and galactorrhea. MRI pituitary was normal. The patient had a known enlarging uterine leiomyoma on serial pelvic ultrasounds (15.2 cm × 9.1 cm × 12.1 cm). The serum prolactin returned to subnormal levels two days postmyomectomy and showed recovery to normal levels in the months following surgery. Immunostaining of the leiomyoma for prolactin was negative. Despite not staining for prolactin, quick resolution of the patient’s hyperprolactinaemia after myomectomy supports the diagnosis of a prolactin-secreting fibroid. A prolactin-secreting leiomyoma should be considered in patients with hyperprolactinaemia and normal pituitary MRI which is refractory to dopamine receptor agonist therapy who also have evidence of a uterine fibroid. In patients wishing to seek fertility, myomectomy should be considered to allow for normal ovulation and possibility of future fertility.

[Introduction] Aripiprazole and olanzapine are atypical antipsychotics. Both drugs can induce metabolic changes; however, the metabolic side effects produced by aripiprazole are more benign. The aim of the study was to evaluate if aripiprazole and olanzapine alter prolactin levels, lipid and glucose metabolism and hepatic, haematological, thyroid and renal function. [Methods] Twenty-four healthy volunteers received a daily oral dose of 10 mg aripiprazole and 5 mg olanzapine tablets for 5 days in a crossover randomised clinical trial and were genotyped for 51 polymorphisms in 18 genes by qPCR. Drug plasma concentrations were measured by LC–MS. The biochemical and haematological analyses were performed by enzymatic methods. [Results] Olanzapine induced hyperprolactinaemia but aripiprazole did not. Dopamine D3 receptor (DRD3) Ser/Gly and ATP binding cassette subfamily B member 1 (ABCB1) rs10280101, rs12720067 and rs11983225 polymorphisms and cytochrome P450 3A (CYP3A) phenotype had an impact on plasma prolactin levels. C-peptide concentrations were higher after aripiprazole administration and were influenced by catechol-O-methyltransferase (COMT) rs4680 and rs13306278 polymorphisms. Olanzapine and the UDP glucuronosyltransferase family 1 member A1 (UGT1A1) rs887829 polymorphism were associated with elevated glucose levels. CYP3A poor metabolizers had increased insulin levels. Volunteers’ weight decreased significantly during aripiprazole treatment and a tendency for weight gain was observed during olanzapine treatment. Triglyceride concentrations decreased as a result of olanzapine and aripiprazole treatment, and varied on the basis of CYP3A phenotypes and the apolipoprotein C-III (APOC3) rs4520 genotype. Cholesterol levels were also decreased and depended on 5-hydroxytryptamine receptor 2A (HTR2A) rs6314 polymorphism. All hepatic enzymes, platelet and albumin levels, and prothrombin time were altered during both treatments. Additionally, olanzapine reduced the leucocyte count, aripiprazole increased free T4 and both decreased uric acid concentrations. [Conclusions] Short-term treatment with aripiprazole and olanzapine had a significant influence on the metabolic parameters. However, it seems that aripiprazole provokes less severe metabolic changes., The study and DK were financed by the H2020 Marie Sklodowska-Curie Innovative Training Network 721236 grant. MN is co-financed by “Consejería de Educación, Juventud y Deporte” PEJ-2018-TL/BMD-11080 grant from “Comunidad de Madrid” and “Fondo Social Europeo”. No Rapid Service Fee was received by the journal for the publication of this article.

It is important to diagnose epilepsy in a timely and accurate manner, and also to distinguish it from non-epileptic conditions. The present study was aimed at determining postictal serum prolactin levels and lactate dehydrogenase (LDH) activities in patients with new-onset seizure admitted to the emergency department in order to assess whether they could be used in the differentiation of epileptic seizure (ES) from nonepileptic seizure (NES).Eighty-five patients were included prospectively in this study. Patients were divided into 2 groups with respect to epilepsy diagnosis, and the final groups were comprised of 36 patients with ES and 49 patients with NES. Blood samples were obtained within 1 hour of seizure.No significant differences between groups were observed in prolactin levels and in the percentage of patients with abnormal prolactin level (P = .569 and .239, respectively). The median LDH activity was significantly higher in those with ES compared with those with NES (P = .031). The percentage of patients with elevated LDH levels was similar between 2 groups (P = .286).This was the first study to examine LDH activities in terms of its role in differentiation of seizure origin in the postictal period in patients hospitalized with seizure. Our study demonstrated that serum LDH activities within 1 hour after the seizure appear to be increased in patients with ES compared with those with NES, suggesting the potential role of LDH activities as a diagnostic tool in distinction of seizure types. Our study supports the hypothesis that LDH-antagonists may have a role in the management of seizure and epilepsy.

Hyperprolactinaemia is the occurrence of an en docrine disorder that leads to an increase in the level of the hormone prolactin (PRL) in the blood above normal levels in cases other than the natural increase in pregnancy and lactation. It may be present as the menstrual disturbances, galactorrhea, sexual dysfunction, gynecomastia, infertility, decreased bone mineral density, and breast cancer. This increase results from several causes that may be pathological such as pituitary tumors, psychological such as stress, or as a result of taking a specific drug such as schizophrenia, anti-vomiting drugs, nerve analgesics, first-generation antipsychotics, hypnotics, and sedatives. Hyperprolactinaemia by metoclopramide was induced in male and female rats to assess the therapeutic effects of alcoholic extracts of sage leaves, marjoram leaves and celery seeds. Through the biochemical analysis of blood hormones, the results showed that treating rats with metoclopramide drug (150 mg / kg / day) for a week had an effect on the positive control group in the occurrence of hyperprolactinaemia compared to the negative control group at the beginning of the experiment. The results indicated that there was a significant effect (P

AimsTo ensure that service users in in-patient secure services have prolactin, vitamin D and HbA1c monitoring as per current best practice guidance.BackgroundService users prescribed antipsychotic medication are at risk of developing raised prolactin levels and metabolic syndrome. In both sexes, long-standing hyperprolactinaemia can lead to low bone mineral density with an increased risk of developing osteoporosis.In recent years there has been increasing controversy on the increase in Vitamin D monitoring despite the poor evidence for complications from vitamin D deficiency in adults. Not undertaking this test in the absence of symptoms will potentially reduce anxiety for service users could save £17 per test and £50 for a 12-week course of Vitamin D supplementation. Local and national guidance indicate Vitamin D monitoring should only be done in symptomatic people.MethodFifty-five service users in the five in-patient wards had their electronic records and pathology results reviewed over a one-year period. All service users were expected to have a minimum of an annual HbA1c and prolactin level but to only have vitamin D monitoring if symptomatic for deficiency.ResultAlthough 100% of service users in MSU were tested, vitamin D testing was consistently undertaken without documented clinical evidence of deficiency. The ranges across all units were: prolactin (72- 1384mU/L), HbA1c (30–90 mmol/mol) and vitamin D (15–124 nmol/L). Local reference ranges are prolactin (53- 360mU/L), HbA1c (Prolactin levels were highest on the male medium secure wards.The other two units had significantly less testing with prolactin and HbA1c levels being the least measured (18% of service users on male LSU and 23% on the female ward respectively). Vitamin D testing on these two wards were 38% on the female ward and 18% on the male ward for both tests.ConclusionNorthside House has a dedicated physical health team and this is likely to explain its 100% score. However, vitamin D testing was being undertaking automatically rather than based on symptoms.The recommendation is to add prolactin and HbA1c to the physical screens done before CPA meetings for all service users prescribed an antipsychotic but to stop Vitamin D testing in the absence of clinical symptoms of vitamin D deficiency.

Different therapeutic strategies are used for lowering prolactin concentrations in patients with psychotic disorders with antipsychotic-induced hyperprolactinaemia. We aimed to examine the evidence from open-label studies and randomized clinical trials (RCTs) that studied four prolactin-lowering therapeutic strategies in people with psychotic disorders and hyperprolactinaemia: 1) switching to prolactin-sparing antipsychotics; 2) adding aripiprazole; 3) adding dopamine agonists; and 4) adding metformin. RCTs were included in a meta-analysis. Effect sizes (Hedges' g) of prolactin reductions with each strategy were calculated. Withdrawal rates were also considered. We identified 26 studies. Nine studies explored switching antipsychotic treatment to aripiprazole (n = 4), olanzapine (n = 1), quetiapine (n = 2), paliperidone palmitate (n = 1) or blonanserin (n = 1). Twelve studies tested the addition of aripiprazole. Six studies explored the addition of cabergoline (n = 3), bromocriptine (n = 2) or terguride (n = 1). We also found one meta-analysis testing the addition of metformin to antipsychotic treatment but no other individual studies. A meta-analysis could only be performed for the addition of aripiprazole, the strategy with the best level of evidence. Five RCTs testing the addition of aripiprazole yielded a significant reduction in prolactin concentration compared to placebo (N = 3) or maintaining antipsychotic treatment (N = 2): Hedges' g was −1.35 (CI 95%: −1.93 to −0.76, p < 0.001). The three placebo-controlled RCTs for aripiprazole addition showed similar withdrawal rates for aripiprazole (10.1%) and placebo (11.5%), without significant differences in the meta-analysis. Our study suggests that, in terms of levels of evidence, adding aripiprazole is the first option to be considered for lowering prolactin concentrations in patients with schizophrenia and hyperprolactinaemia.

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.

Introduction: Hyperprolactinaemia, 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. Aims: To 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. Methods: In 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. Results: We 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. Conclusion: This study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone-induced hyperprolactinaemia.

Summary Papillary thyroid gland carcinoma is the most common type of malignancy of the endocrine system. Metastases to the pituitary gland have been described as a complication of papillary thyroid cancer in few reported cases since 1965. We report the case of a 68-year-old female patient with a well-differentiated form of thyroid gland cancer. Despite it being the most common malignant cancer of the endocrine system, with its papillary form being one of the two most frequently diagnosed thyroid cancers, the case we present is extremely rare. Sudden cardiac arrest during ventricular fibrillation occurred during hospitalization. Autopsy of the patient revealed papillary carcinoma of the thyroid, follicular variant, with metastasis to the sella turcica, and concomitant sarcoidosis of heart, lung, and mediastinal and hilar lymph nodes. Not only does atypical metastasis make our patient’s case most remarkable, but also the postmortem diagnosis of sarcoidosis makes her case particularly unusual. Learning points: The goal of presenting this case is to raise awareness of the clinical heterogeneity of papillary cancer and promote early diagnosis of unexpected metastasis and coexisting diseases to improve clinical outcomes. Clinicians must be skeptical. They should not fall into the trap of diagnostic momentum or accept diagnostic labels at face value. Regardless of the potential mechanisms, clinicians should be aware of the possibility of the coexistence of thyroid cancer and sarcoidosis as a differential diagnosis of lymphadenopathy. This case highlights the importance of the diagnostic and therapeutic planning process and raises awareness of the fact that one uncommon disease could be masked by another extremely rare disorder.

Hyperprolactinaemia is a common endocrine abnormality in patients with kidney failure. A 43-year-old female, known with kidney failure on maintenance haemodialysis, was referred with symptomatic hyperprolactinaemia. Biochemical investigations revealed a markedly elevated serum prolactin level. Magnetic resonance imaging of the brain (without gadolinium) demonstrated a pituitary macroadenoma. The patient was started on cabergoline therapy. This case discusses hyperprolactinaemia in kidney failure and highlights the importance of investigating markedly elevated prolactin levels. In cases where patients have galactorrhoea, headaches and/or visual disturbances, clinicians should be alert to the possibility of a prolactin-secreting pituitary tumour.

Objectives: This study assessed the association between serum prolactin (PRL) concentration and aggression in female patients with schizophrenia. Methods: Female patients with schizophrenia (N = 120) were diagnosed using SCID-5 based on the DSM-5 criteria. They were sampled at the University Psychiatric Hospital Vrapce during the period from March 2017 to March 2019. Aggression was evaluated using the Positive and Negative Syndrome Scale (PANSS), and Overt Aggression Scale (OAS). Patients were subdivided into aggressive and non-aggressive groups. PRL was determined in serum using electrochemiluminescence (ECLIA) method. Results: Aggressive patients with schizophrenia had significantly (p < 0.0001) increased PRL concentration compared to non-aggressive patients. Higher PRL concentration was significantly (p < 0.0001) associated with pronounced aggressive symptoms determined by the OAS scores. When patients were subdivided into those who were treated with risperidone, haloperidol, paliperidone, amisulpride, and a group that was not treated with these antipsychotics, aggressive patients in both groups had significantly higher PRL concentrations than non-aggressive patients. Higher antipsychotic dose was related to increased PRL concentration (p = 0.004). Conclusions: Our findings suggest that higher PRL is significantly associated with aggression, irrespective of the antipsychotic medication, in female patients with schizophrenia.

© 2020 The Author(s)., The data presented in this paper describe supplementary material to the article entitled “Pharmacological treatment strategies for lowering prolactin in people with a psychotic disorder and hyperprolactinaemia: a systematic review and meta-analysis” [1]. Although raw data was published on the original article, additional raw data has been included in the current paper (new tables with socio-demographic and clinical characteristics of the samples of the studies included in the systematic review). Supplementary data also include the PICO scheme of the systematic review, PRISMA checklist, flow diagram, an explanation of the method for obtaining prolactin concentrations from published figures when data was only available in figures, list of the selected studies, risk of bias summary of all five randomized clinical trials evaluating the addition of aripiprazole for lowering prolactin (included in the meta-analysis in the original article). Extra analyses, figures and R code of the meta-analysis have been also included. Meta-analysis of randomized clinical trials (RCTs) considering aripiprazole addition for lowering prolactin in people with a psychotic disorder and hyperprolactinaemia were conducted with two softwares: 1) R and the metaphor package (for the meta-analysis of the primary outcome [prolactin reduction]); 2) MedCalc version 18.11 (for the meta-analysis of the secondary outcome [withdrawal rates]). Data from a sensitivity analysis (repeating the meta-analysis with only placebo-controlled RCTs) has been also included in the current article., Javier Labad and Itziar Montalvo have received an Intensification of the Research Activity Grant by the Health Department from the Generalitat de Catalunya (SLT006/17/00012 and SLT008/18/00074). Javier Labad has received an Intensification of the Research Activity Grant by the Instituto de Salud Carlos III (INT19/00071).