A case report on azathioprine-induced euprolactinemic galactorrhea.

Galactorrhea is characterized as an inappropriate discharge of milk-containing fluid from the breast. It has various causes including physiological and pathological. It may also be caused by many drugs. Although galactorrhea is usually associated with increased serum prolactin levels, it has been reported to occur in the absence of hyperprolactinemia. Cases of azathioprine-induced galactorrhea with normal prolactin level in a 22-year-old female patient with prurigo have been reported. It was noticed that the patient had no history of galactorrhea in the past.

Frequency of Macroprolactin in Hyperprolactinemia.

OBJECTIVE: To determine the frequency of Macroprolactin (MaPRL) in patients with increased total prolactin and its clinical and financial impact. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from March to May 2015. METHODOLOGY: Patients with high total prolactin were screened by polyethylene glycol (PEG) precipitation for determination of MaPRL. Clinical history, imaging work-ups, and cost incurred in further investigations were collected by telephonic interview after verbal consent. Patients were stratified into true hyperprolactinemia and macroprolactinemia after PEG treatment, based on monomeric prolactin levels. Medical records of cases registered with AKUH were reviewed to confirm the diagnosis. RESULTS: Two hundred and thirty-nine patients were identified with high prolactin levels. Macroprolactinemia was identified in 145 (60.7%) and true hyperprolactinemia in 94 (39.3%) patients. Galactorrhea was significantly more in true hyperprolactinemic females (p=0.022), followed by visual disturbances (p=0.01) and headache (p=0.006). Moreover, as majority of population were females, the clinical features in the macroprolactinemia group as compared to true hyperprolactinemic group were mostly related to non-pituitary causes like drug intake [42.5% (54) vs. 37% (30)], heat intolerance due to thyroidal illness [41.7% (53) vs. 38.3% (31)] and surgery [26.8% (34) vs 22.2% (18)] in females. Further radiological workup (MRI, CT) were conducted in 35 (37.2%) patients with true hyperprolactinemia. Twenty-one (60%) of the patients were confirmed to have pituitary adenomas. In eight (5.5%) patients with MaPRL, only one had pituitary microadenoma on radiological workup. Total cost impact on the basis of investigations, was significantly higher in the group undergone imaging, despite 7 out of 8 individuals found to have normal imaging results. The median total cost in true hyperprolactinemic group undergone imaging was Rs. 4370 (IQR=2412.5, 22850) as compared to macroprolactinemic groups; Rs. 3,250 (IQR=2150, 4278). There was significant difference in the cost burden of both the groups (p <0.001). CONCLUSION: High frequency of MaPRL was identified in patients with hyperprolactinemia. Screening with PEG precipitation in hyperprolactinemic sera is simple and cost-effective.

Impact of macroprolactin on galactorrhea and the rate of patients possibly affected by macroprolactin.

The clinical influence of macroprolactin (MPRL) is not clearly understood and the rate of patients potentially affected by MPRL is unknown. We investigated the influence of MPRL on the onset of galactorrhea and estimated the rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea. Data of patients with obstetric or gynecological symptoms who had undergone PRL fractionation testing were retrospectively analyzed. To evaluate factors influencing galactorrhea, a multivariate logistic regression analysis was performed and the adjusted odds ratios of MPRL for galactorrhea were calculated. Cutoff values for the total PRL level and the proportion of MPRL fractions for galactorrhea were determined by ROC analysis using a multivariate logistic model. The prevalence of patients with a proportion of MPRL fraction greater than or equal to the cutoff value for galactorrhea was estimated. The median proportion of MPRL fraction was 30.1% and increased as PRL level increased. Total PRL and MPRL had a significant influence on the onset of galactorrhea and the adjusted odds ratio was 1.09 in total PRL and 0.94 in MPRL. The rate of patients with a proportion of MPRL fraction that may possibly affect galactorrhea was estimated to be 33.5% of the study population, and thus found to be twelve times or more the number of macroprolactinemia patients. Future prospects for hyperprolactinemia may require diagnostic criteria using free prolactin levels and so MPRL fraction measurement is important for the diagnosis and treatment of patients with obstetric and gynecological symptoms.

Paraneoplastic Galactorrhea in Childhood T-ALL: An Evaluation of Tumor-derived Prolactin.

T-cell acute lymphoblastic leukemia (T-ALL) comprises 15% of childhood leukemia. Although multiagent pulse chemotherapy has improved event-free survival in recent decades, the lack of reliable prognosticators and high rate of relapse remain a challenge. Described is a novel discovery of tumor-derived hyperprolactinemia in childhood T-ALL through a case associated with paraneoplastic galactorrhea. Prolactin production by tumor cells, although a rare phenomenon, is previously demonstrated in several adult cancers and 2 pediatric malignancies with unknown implications. This is the first report demonstrating tumor-derived prolactin in pediatric T-ALL and offers potential as a disease marker and therapeutic drug target.

A case of galactorrhea during paroxetine treatment.

Paroxetine is one of the selective serotonin reuptake inhibitor antidepressant drugs. Galactorrhea can be seen during antidepressant treatments. There are a few reports in literature on paroxetine use and related prolactin level changes. We present a case that was receiving paroxetine in whom despite low blood levels of the drug, hyperprolactinemia, and galactorrhea was found. We present a case that was receiving paroxetine despite low drug blood levels, hyperprolactinemia, and galactorrhea was found in this article.

The risk of elevated prolactin levels in pediatric patients exposed to antipsychotics for the treatment of schizophrenia and schizophrenia spectrum disorders: protocol for a systematic review and meta-analysis.

BACKGROUND: Antipsychotic medications, particularly second-generation antipsychotics, are increasingly being used to alleviate the symptoms of schizophrenia and other severe mental disorders in the pediatric population. While evidence-based approaches examining efficacy and safety outcomes have been reported, no review has evaluated prolactin-based adverse events for antipsychotic treatments in schizophrenia and schizophrenia spectrum disorders. METHODS/DESIGN: Searches involving MEDLINE, EMBASE, CENTRAL, PsycINFO, and clinical trial registries (ClinicalTrials.gov, Drug Industry Document Archive [DIDA], International Clinical Trials Registry Platform [ICTRP]) will be used to identify relevant studies. Two reviewers will independently screen abstracts and relevant full-text articles of the papers identified by the initial search according to the prospectively defined eligibility criteria. Data extraction will be conducted in duplicate independently. Pairwise random effects meta-analyses and network meta-analyses will be conducted on individual drug and class effects where appropriate. DISCUSSION: This systematic review will evaluate prolactin-based adverse events of first- and second-generation antipsychotics in the pediatric population with schizophrenia and schizophrenia spectrum disorders. It will also seek to strengthen the evidence base of the safety of antipsychotics by incorporating both randomized controlled trials and observational studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009506.

Burns, hypertrophic scar and galactorrhea.

An 18-year-old woman was admitted to Motahari Burn Center suffering from 30% burns. Treatment modalities were carried out for the patient and she was discharged after 20 days. Three to four months later she developed hypertrophic scar on her chest and upper limbs. At the same time she developed galactorrhea in both breasts and had a disturbed menstrual cycle four months post-burn. On investigation, we found hyperprolactinemia and no other reasons for the high level of prolactin were detected.She received treatment for both the hypertrophic scar and the severe itching she was experiencing. After seven months, her prolactin level had decreased but had not returned to the normal level. It seems that refractory hypertrophic scar is related to the high level of prolactin in burns patients.

Clinical and radiological findings in macroprolactinemia.

Hyperprolactinemia is the most common abnormality of the hypothalamic-pituitary axis. The aim of this study was to investigate the clinical and radiological features of patients with macroprolactinemia. The study population consisted of patients with elevated serum prolactin (PRL) concentrations who presented to our Endocrinology outpatient clinic. Detection of macroprolactin (macroPRL) was performed using the polyethylene glycol precipitation method. Patients in which macroPRL made up more than 60% of total PRL levels were stratified into the macroPRL group, while the remaining patients were placed in the monomeric prolactin (monoPRL) group. A total of 337 patients were enrolled with a mean age of 33.8 ± 10.8 (16-66) years and a male/female ratio of 29/308. Eighty-eight of the patients (26.1%) had an elevated macroPRL level. The mean age in the monoPRL group was higher than in the macroPRL group (35.0 ± 10.1 vs. 30.7 ± 9.8, P = 0.016). The mean PRL levels (ng/ml) in the macroPRL and monoPRL groups were similar (168.0 ± 347.0 vs. 238.8 ± 584.9, P = 0.239). Frequency of amenorrhea, infertility, irregular menses, gynecomastia, and erectile dysfunction were also similar in both groups. More patients in the macroPRL group were asymptomatic compared to the monoPRL group (30.2 vs. 12.0%, P = 0.006). Compared to the macroPRL group, the monoPRL group had a higher frequency of galactorrhea (39.2 vs. 57.1%, P = 0.04) and abnormal magnetic resonance imaging findings (65.3 vs. 81.1%, P = 0.02). Elevated macroPRL levels should be considered a pathological biochemical variant of hyperprolactinemia that may present with any of the conventional symptoms and radiological findings generally associated with elevated PRL levels.

A case of sibutramine-induced hyperprolactinemia.

INTRODUCTION: Several drugs may cause hyperprolactinemia, especially antipsychotic drugs and prokynetic drugs. Serum prolactin concentrations increase within hours after acute administration of these drugs and return to normal within two to four days after cessation of chronic therapy. So far, sibutramine, a sympathomimetic drug used in the management of obesity, was not described to be associated with altered prolactin levels. OBJECTIVE: The purpose of this study is to present a case of sibutramine-induced hiperprolactinemia. CASE REPORT: A 38-year-old white female patient seeks medical attention complaining of weight gain (Body mass index: 35) associated with anxiety. She started sibutramine treatment and presented with amenogalactorrhea. Hyperprolactinemia was diagnosed (prolactin of 46 and 89.6 ng/mL) with normal thyroid, renal and hepatic function, and a negative pregnancy test. A sella MRI was performed and sibutramine was suspended. Prolactin levels returned to normal within 15 days of sibutramine cessation and remained normal within 90 days of follow-up, with resolution of the amenogalactorrhea syndrome. CONCLUSION: sibutramine may be considered in differential diagnosis of drug-induced hyperprolactinemia.

Hyperprolactinaemia during treatment with paliperidone.

OBJECTIVE: The aim of this paper is to highlight the association between antipsychotic medication, in this instance paliperidone, and hyperprolactinaemia, and discuss the impact of this adverse effect on patient management. METHOD: Four patients with paliperidone-induced hyperprolactinaemia are described with a brief review of the literature. RESULTS: Four female patients aged between 20 and 50 years developed hyperprolactinaemia 3 weeks to 4 months after commencement of treatment with paliperidone. The levels were significantly raised above the normal upper limit of 500 mIU/L, ranging between 1500 and 3996 mIU/L, and returned to within the normal range after cessation of the medication (82-381 mIU/L). Two of the patients were asymptomatic despite significant elevation of prolactin; two experienced galactorrhoea, a distressing adverse effect. Subsequent management was significantly affected. CONCLUSIONS: Routine standardized monitoring of prolactin levels may guide treatment choice, avoiding potential disruption to the therapeutic relationship, enhancing compliance with future medication and preventing negative treatment outcomes. Detailed education should accompany the monitoring process and include discussion of the risks of associated adverse effects of antipsychotic medications versus the benefit of significant symptom relief.

[Irregular secretion of prolactin in infertile women with normoprolactinemic galactorrhea]. / Secreción irregular de prolactina en mujeres infértiles con galactorrea normoprolactinémica.

BACKGROUND: Abnormal frequency and pulse amplitud of prolactin secretion in micro and macroprolactinomas has been atributed to a dysfunctional tumoral lactotrope. Previous evidence suggests that non tumoral hyperprolactinemia is caused by a hypothalamic dysfunction. The regularity of prolactin secretion has not been studied with cuantitative methods in patients with normoprolactinemic galactorrhea (NPG) which could be considered an entity that precedes non tumoral and tumoral hyperprolactinemia. OBJECTIVE: To analyze the 24-hour prolactin secretion pattern and its secretion regularity in a group of infertile women with normoprolactinemic galatorea. PATIENTS AND METHODS: A transversal-comparative study was carried out in 6 infertile women with normoprolactinemic galactorrhea and 4 healthy women as controls. The 24 hour prolactin profile, the ratio night time mean concentration/daytime mean concentrattion (NM/DM ratio) and apparent entropy (Ap En, Ap En ratio) were compared in the two groups. RESULTS: Blunting of the nyctohemeral rythm and nocturn hyperprolactinaemia occurred in patients with normoprolactinemic galactorrhea (NPG). NM/DM ratio was lower in patients with NPG than in controls (1.28 +/- 0.25 vs. 1.75 +/- 0.05; p= 0.01). Higher irregularity of prolactin secretion was found in patients with NPG (ApEn: 0.853 +/- 0.158 vs 0.608 +/- 0.171, p=0.04; Ap En ratio: 0.839 +/- 0.11 vs 0.661 +/- 0.14; p=0.04). CONCLUSIONS: The irregularity of prolactin secretion in patients with NPG is not dependant on the presence of a pituitary tumour which suggests that a hypothalamic dysfunction underlies this condition. An irregular secretion and a higher daily mass production of prolactin in patients with NPG could explain both galactorrhea and infertility.

A case with euprolactinemic galactorrhea induced by escitalopram.

Endocrine and reproductive side effects of serotonergic antidepressants are uncommon and galactorrhea is only rarely mentioned among SSRI-related side effects. Perhaps through suppression of dopamine neurotransmission releasing prolactin from tonic inhibitor control of dopamine, serotonin-enhancing antidepressants may result in a rise in prolactin levels. However, we here describe a case of euprolactinemic galactorrhea induced by the SSRI escitalopram and discuss potential mechanisms of action.

Risperidone-induced symptomatic hyperprolactinaemia in adolescents.

Studies performed in adult patients unambiguously demonstrate a marked effect of risperidone on prolactin blood levels, with possible clinical effects related to hyperprolactinemia, such as gynecomastia and galactorrhea. However, the largest study performed in children and adolescents showed a weak effect of risperidone on prolactin concentrations during short-term treatment and a negligible effect during long-term treatment, which was probably because of the relatively low dosages of risperidone used [approximately 0.04 mg/(kg x d)]. Among the 10 psychotic adolescents treated with risperidone in our unit, we had 3 cases of gynecomastia in 3 male patients and 2 cases of galactorrhea in 2 female patients. The prolactin blood levels in these cases and in 3 other patients without apparent prolactin-related side effects were all above the normal range (median, 59 ng/mL; range, 30-123 ng/mL). Thus, risperidone administered to adolescents at doses commonly used for the treatment of psychotic symptoms can strongly increase prolactin levels, with clinical consequences such as gynecomastia and/or galactorrhea. Given that the long-term effects of antipsychotic drug-induced hyperprolactinemia are not well documented, especially regarding osteopenia, infertility, growth, and pubertal delay, risperidone should be administered with caution to children and adolescents.

Clinical and radiological features of patients with macroprolactinaemia.

OBJECTIVES: Macroprolactin is a complex of prolactin (PRL) and IgG and may account for a significant proportion of cases of 'idiopathic hyperprolactinaemia'. In this study, we sought to determine the prevalence and clinical features of macroprolactinaemia in patients diagnosed with hyperprolactinaemia in our region, with a view to determining how patients with macroprolactinaemia should be investigated and managed. PATIENTS AND METHODS: An Immuno-1 automated immunoassay system with polyethylene glycol (PEG) precipitation was used to identify macroprolactin, with a recovery of 700 mU/l. The clinical records of 51 (44 female) were available for retrospective review. RESULTS: The mean (range) age of patients was 39.5 (18-82) years. The median (range) concentrations for the various forms of PRL were: total PRL 1130 mU/l (728-5116), monomeric PRL 240 mU/l (50-656) and macroprolactin 895 mU/l (381-4854). Classical symptoms of hyperprolactinaemia were present in 39% of patients, although in many there were other possible explanations for their symptomatology. Pituitary adenomas were identified in six out of 36 people who underwent neuroimaging. Five of these patients had a microadenoma and one had a 10-mm macroadenoma (although, in this patient macroprolactin was identified after the discovery of the tumour). There was no relationship between macroprolactin concentrations and the presence of hyperprolactinaemic symptoms or neuroimaging abnormalities. CONCLUSIONS: Macroprolactinaemia is a common occurrence in patients with hyperprolactinaemia, but associated symptomatology may not necessarily be linked. The neuroimaging abnormalities were also probably incidental findings and it is questionable whether neuroimaging is necessary when significant macroprolactinaemia is identified and the concentration of monomeric PRL is not elevated (using the Immuno-1 assay system, following PEG precipitation).