Idiopathic Hyperprolactinemia Research Articles

The homeo-FIT-prolactin hypothesis: the role of prolactin in metabolic homeostasis - association or causality?

The homeo-fit-prolactin hypothesis proposes a causal metabolic role for prolactin with hypoprolactinemia and hyperprolactinemia leading to adverse metabolic alterations. However, prolactin within the normal range and up to four times the upper reference limit may be a consequence of metabolic adaption and have a positive metabolic role similar to increased insulin in pre-diabetes. As a consequence, drugs that would increase prolactin levels within this threshold may hold promising effects, particularly for patients with type 2 diabetes. A documented positive metabolic effect of prolactin just above the normal threshold would not just be of benefit to patients with diabetes but assist in the decision to treat mild hyperprolactinemia in other patient groups as well, e.g. drug-induced hyperprolactinemia or idiopathic hyperprolactinemia. Prolactin receptors are present in the pancreas, liver, and adipose tissue, and pre-clinical studies suggest a positive and causal effect of prolactin on the gluco-insulinemic profile and lipid metabolism. This narrative review examines the evidence for the homeo-fit-prolactin hypothesis with a particular focus on results from human studies.

Usefulness of prolactin levels in predicting the etiology of hyperprolactinemia in a cohort of 770 patients.

Determining the etiology of hyperprolactinemia is fundamental for selecting the most appropriate treatment strategy. The aim of this study was to evaluate the usefulness and accuracy of prolactin levels in predicting the etiology of nonphysiological hyperprolactinemia. In this retrospective study, we reviewed medical records of patients with nonphysiological hyperprolactinemia seen at two neuroendocrine reference centers located in Recife, Brazil, from January 2000 to December 2019. The study included 770 patients aged 12-73 years (65% female). The three most frequent etiologies of hyperprolactinemia were prolactinomas (n = 263; 34.2%), drug-induced hyperprolactinemia (n = 160; 20.8%), and macroprolactinemia (n = 120; 15.6%). The highest mean prolactin levels were observed in cases of prolactinomas and idiopathic hyperprolactinemia. Most patients with hyperprolactinemia due to other etiologies had prolactin levels < 100 ng/mL, but these levels were also found in 16.5% of patients with microproplactinomas and in 20% of those with idiopathic hyperprolactinemia. Likewise, prolactin levels largely overlapped among patients with microprolactinomas, macroprolactinemia, and drug-induced hyperprolactinemia. Notably, prolactin levels > 250 ng/mL enabled a clear distinction between the etiologies of macroprolactinoma and nonfunctioning pituitary adenoma. Moreover, prolactin levels > 500 ng/mL were highly suggestive of macroprolactinomas, although they were also found in very few patients (<2%) with microprolactinomas or drug-induced hyperprolactinemia. Despite considerable overlap in prolactin levels among the different etiologies of hyperprolactinemia, values > 250 ng/mL allowed a clear distinction between macroprolactinomas and nonfunctioning pituitary adenomas. Furthermore, prolactin levels > 500 ng/mL were almost exclusively found in patients with prolactinomas.

Hyperprolactinemia of various genesis in premenopause: effect on cardiovascular risks, a practical aspect

The pathological aspects of hyperprolactinemia have been well studied to date and primarily affect changes in the reproductive system. Regardless of the genesis of hyperprolactinemia, negative changes include, first of all, dysmenorrhea and hyperan drogenism. Changes in the mammary glands include galactorrhea, mastopathy, and the development of breast cancer. The pathological effects of hyperprolactinemia on other organs and systems, including the cardiovascular system, have been studied less. Few existing studies suggest that elevated prolactin levels can potentially affect cardiovas cular risks and provoke myocardial remodeling, arterial hypertension, hyperhomocys teinemia, and disorders of the plasma lipid profile. Menopausal women are particularly vulnerable in this regard, as the cardioprotective role of estrogens is significantly re duced during this period. In this article, we examined the effect of hyperprolactinemia on the formation of cardiovascular disorders in premenopausal women. The purpose of the study was to evaluate the effect of hyperprolactinemia on the genesis of cardiovascular pathology in premenopausal women. Materials and methods: three groups of premenopausal patients were examined. The patients of the first group (n=26) had previously been diagnosed with pituitary adenoma and were treated with cabergoline, maintaining the target prolactin level for at least two years. According to pituitary MRI, prolactinoma and elevated prolactin levels were de tected in the patients of the second group (n=21), but these patients did not take prolac tin-lowering therapy for various reasons. The third group consisted of the patients with idiopathic hyperprolactinemia who did not receive prolactin-lowering therapy (n=19). The patients of all three groups underwent general clinical examination, determination of the daily blood pressure profile, ECG, echocardiography, determination of the level of lipidogram, homocysteine, and other markers of cardiovascular risk. The results of the study showed that regardless of its genesis, pathological hyperprolactinemia influences the development of cardiovascular pathology in premenopausal women.

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

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

Prolactin Monomeric Polyethylene Glycol Measurement Method and Study of Reference Value Verification

Purpose: Prolactin in the blood is separated into three types, and over 90% of prolactin presents as a double monomer (23 KDa). Rarely, it can exist in the size of big prolactin (150 KDa), which is called macroprolactin and is known as an autoantibody complex. When macroprolactin accounts for more than 60% of prolactin in the blood, it is called macroprolactinemia. The presence of such macroprolactin was first reported in a patient with hyperprolactinemia but without typical symptoms. Macroprolactinemia is emerging as an important cause of idiopathic hyperprolactinemia. The polyethylene glycol (PEG) precipitation method using the property of precipitating large-molecular-weight proteins is simple and recently has been widely used as a screening test. The results are in good agreement with the results of gel chromatography. The purpose of this study was to confirm the measurement method and reference value verification of monomeric prolactin in blood prolactin using the PEG precipitation method. Materials and Methods: For 40 examinees who visited the Gangnam Center of Seoul National University Hospital in 2021, the prolactin level was verified using radioimmunoassay (RIA). For macroprolactinemia PEG precipitation method, 25% PEG (molecular weight 6000kDa) solution and serum were mixed in equal amounts in a test tube, then left at room temperature for 20 minutes and centrifuged at 4℃ for 30 minutes (1500g). The prolactin level was measured in the supernatant. Results : After confirming that more than 90% of the 40 tested samples within the reference range &lt;25 ng/mL, the same value as the reference value for prolactin was applied. Since the concentration of monomeric prolactin in serum from which macroprolactin has been removed from blood is diluted 1:1 with PEG, our laboratory is currently reporting the result by multiplying the result by a dilution factor of 2. Conclusion: Radioimmunoassay using PEG precipitation method using the property of precipitating large molecular weight proteins is simple and effective for quantitative measurement of monomeric prolactin in blood prolactin.

Etiopathogenetic features of hyperprolactinemia in childhood

In recent years, the problem of hyperprolactinemia in children remains relevant because it is one of the most common pathologies of the hypothalamic-pituitary system, causing impaired fertility and reproductive function in adulthood. According to population studies, its incidence is 0.5 % in females, exceeding this figure in males by 10 times. Prolactin has: immunomodulatory effect, enhancing lymphocyte proliferation, phagocytic capacity of macrophages, IgA synthesis; analgesic effect; promotes postnatal growth of the body by inducing the activity of genes associated with growth; activates the proliferation of keratinocytes, epithelial cells of the prostate; participates in the regulation of metabolism, water-electrolyte balance, inhibiting the excretion of potassium and sodium ions by the kidneys; influences human behavior by accelerating neurogenesis, memory, learning and providing neuroprotection; induces surfactant production; stimulates lipogenesis. Prolactin levels increase due to physiological hyperestrogenemia, which blocks the inhibitory effect of dopamine on prolactin secretion and occurs during lactation, pregnancy and some other physiological states. Pathological hyperprolactinemia occurs in children with secondary hypogonadotropic hypogonadism, organic lesions of the suprasellar area of the brain and may be secondary (symptomatic). In the etiological structure of hyperprolactinemia syndrome, the largest proportion (60 %) in children and adolescents belongs to prolactinomas (pituitary adenomas that secrete prolactin), idiopathic hyperprolactinemia (22.7 %) and iatrogenic hyperprolactinemia induced by 6 drugs (4 % of cases). Given that the lion’s share of hyperprolactinemia in childhood is associated with the presence of pituitary prolactinoma, characterized by latent gradual progression of reproductive disorders, growth processes and neurological symptoms, the objective of this article is to focus on the pleiotropic effects of prolactin in the body, which controls more than 300 biological functions, epidemiological, etiological and pathogenetic mechanisms, on the features of the clinical classification of hyperprolactinemia to form a modern understanding of this problem.

Evaluation of hyperprolactinemia risk factors in infertile women referred to Yazd Infertility Center: A cross-sectional study.

BackgroundHyperprolactinemia is one of the most common causes of infertility in women. The prevalence of pituitary tumors is 25-30% among infertile participants with hyperprolactinemia.Objective The aim of this study was to describe the causes of hyperprolactinemia in infertile women referred to Yazd Infertility Center.Materials and MethodsThis cross-sectional study was conducted with 182 infertile women with hyperprolactinemia who were referred to Yazd Infertility Center from February 2018 to October 2019. Serum prolactin was assessed by the human prolactin ELISA kit according to the Padtan Gostar Isar protocol. The age, duration of infertility, causes of hyperprolactinemia, and type of infertility treatment were noted. The MRI findings were added.Results The mean age of participants was 28.9 0.36 yr and the prolactin level was 76 8.97 ng/ml. The etiology of hyperprolactinemia among the study participants was 35 participants (19.2%) with pituitary adenoma, 47 participants (25.8%) with polycystic ovary syndrome, 14 participants (7.7%) with pituitary adenoma and polycystic ovary syndrome, and 86 participants (47.3%) with idiopathic hyperprolactinemia. The results of this study showed that there was no statistically significant difference between the mean prolactin levels in participants with different causes of hyperprolactinemia (p = 0.31).ConclusionIdiopathic hyperprolactinemia and polycystic ovary syndrome are the most common reasons for hyperprolactinemia.

Abstract #1002789: Idiopathic Hyperprolactinemia and Elevated Adrenocorticotropic Hormone (ACTH) in a Male with Gynecomastia

Gynecomastia is characterized by a benign proliferation of glandular breast tissue in men. Non-physiologic causes of gynecomastia are a result of various medical conditions, medication use, or substance use. We report a case of a 31-year-old male presenting with gynecomastia in the setting of hyperprolactinemia and elevated ACTH with no underlying pathological condition.

True hyperprolactinemia in men without visible pituitary adenoma.

Men with mild to moderate hyperprolactinemia rarely present with normal pituitary on MRI with no visible adenoma, a condition entitled also "idiopathic hyperprolactinemia" or "non-tumoral hyperprolactinemia". We have characterized a cohort of hyperprolactinemic men with normal pituitary imaging. We have identified 13 men with true hyperprolactinemia and normal pituitary MRI. Baseline clinical and hormonal characteristics and response to medical treatment were retrospectively retrieved from medical records. Mean age at diagnosis was 51 ± 16 years (range, 20-77); mean serum prolactin level at presentation was 91 ng/ml (range, 28-264), eight men presented with low baseline testosterone. Initial complaints leading to diagnosis included sexual dysfunction in ten men and gynecomastia in five. All patients were treated with cabergoline, except for one who was given bromocriptine; none required pituitary surgery. All patients normalized prolactin and testosterone with subsequent clinical improvement reported by most men. Currently, after a mean follow-up of 72 months, ten patients continue treatment with caborgoline (median weekly dose, 0.25 mg), whereas three men discontinued treatment. Men with symptomatic hyperprolactinemia may rarely present with normal pituitary imaging. Medical treatment can lead to hormonal improvement with clinical benefit.

Is idiopathic mild hyperprolactinemia a cardiovascular risk factor?

There is a strong relationship between arterial stiffness and endothelial dysfunction and hypertension. How arterial stiffness is affected in elevated PRL conditions is uncertain. Biological action of prolactin contributing to the atherosclerotic process is a new research area. We aimed at investigating cardiovascular risk predictability by conducting arterial stiffness measurement in patients with idiopathic hyperprolactinemia. The biochemical parameters and arterial stiffness analyses of 54 patients with idiopathic hyperprolactinemia, who had applied to our polyclinic in 2017 and 2018, and 55 healthy volunteers having similar characteristics with regard to age, sex and body mass index. The median prolactin level of the idiopathic hyperprolactinemia patients with a median age of 31 was found to be 45 ng/mL. The peripheral and central blood pressures and pulse wave velocities (PWV) of both the patient group and the control group were found to be similar. Any relations between prolactin levels and blood pressure and arterial stiffness could not be found. Our study showed that arterial stiffness did not increase in young patients with idiopathic mild hyperprolactinemia. However, the long-term effects of mildly elevated prolactin levels are unknown. Prospective randomized studies are required, that could reveal more clearly the prolactin-cardiovascular risk relation, and the clinical effects of extra-pituitary hyperprolactinemia.

Prolactin Level in Polycystic Ovary Syndrome (PCOS): An approach to the diagnosis and management.

Introduction:In spite of the increasing prevalence of polycystic ovary syndrome, there are restricted studies about different features of PCOS. In this study, we evaluate serum prolactin levels in PCOS patients and compare clinical features and hormone levels between patients with hyperprolactinemia and normal levels of prolactin.Methods:Serum prolactin level in 330 PCOS patients were evaluated. If the prolactin levels were normal (equal to or less than 25 ng/ml) the patient was considered normal. If the prolactin levels were >25 ng/ml, then the level was measured by Polyethylene glycol (PEG) precipitation method to detect macroprolactinemia. Furthermore, brain MRI was done in case of hyperprolactinemia to discover pituitary adenoma.Results:Among 330 patients with PCOS, 208 (63.4%) had normal prolactin levels and 122 (37%) patients had hyperprolactinemia. Among hyperprolactinemic patients, 72 (59%) had normal prolactin levels after PEG precipitation and 33 (27%) patients had pituitary adenoma in their brain MRI and 17 (13%) patients were considered as idiopathic hyperprolactinemia with normal MRI. Further, higher levels of LH and LH/FSH ratio and lower estradiol levels were observed in patients with normal prolactin levels. Also, menstrual disorders were more prevalent among patients with pituitary adenoma.Conclusions:Investigating increased level of prolactin in PCOS patients is recommended to detect the causes of hyperprolactinemia, especially macroprolactinemia. (www.actabiomedica.it)

Reproductive function and pregnancy outcomes in women treated for idiopathic hyperprolactinemia: A non-randomized controlled study.

BackgroundFew studies have focused to determine the peculiarities of the course of pregnancy and pregnancy outcomes after treatment in women with idiopathic hyperprolactinemia.ObjectiveTo determine the peculiarities of the course of pregnancy and pregnancy outcomes in women treated for idiopathic hyperprolactinemia, with history of infertility and/or recurrent pregnancy loss.Materials and MethodsA non-randomized controlled study was conducted at the Center for Reproductive Medicine “Universe" and Medical Clinic “Medhealth” during 2016-2018, involving 96 women with idiopathic hyperprolactinemia, aged 20-44 yr with infertility and/or a history of recurrent pregnancy loss. Prolactin (PRL), follicle-stimulating hormone, luteinizing hormone, estradiol (E2), free testosterone, and progesterone were studied in blood serum using immunoassay analysis method. Before the occurrence of pregnancy, hyperprolactinemia was treated with bromocriptine. Dydrogesterone was used to support the luteal phase.ResultsPRL levels decreased significantly and normalized within two-five months, regular menstrual cycle was restored in two-four months, ovulation was restored in three-seven months, and pregnancy was achieved in three-fourteen months. E2 and progesterone levels increased significantly (p 0.001). Prior to the treatment, significant negative correlation between PRL and E2 (r = -0.386, p = 0.007), PRL and progesterone (r = -0.420, p = 0.003) was detected. Threatened early abortion prevailed among pregnancy complications. Pregnancy loss in the first trimester was recorded in 3.12% of cases.ConclusionPregnancy outcomes in women with idiopathic hyperprolactinemia are improved by prolonged and continuous treatment with bromocriptine before pregnancy and administration of dydrogesterone in support of the luteal insufficiency.

Endocrine Markers of Fertility Potential in Reproductive Age Women with Idiopathic Hyperprolactinemia

Background: Hyperprolactinemia (HP) is a common endocrine gynecological disorder in women of reproductive age manifested with menstrual irregularity and sterility subfertility among the majority of women with this disorder.&#x0D; Objective: The aim of this study was to assess the endocrinal markers of inferility in premenopausal women with idiopathic hyperprolactinemia.&#x0D; Materials and Metahodology: The study included 82 women: 27 healthy women, 22 fertile women with idiopathic HP and 33 patients with endocrine sub fertility with idiopathic HP. All women underwent a standard history taking, clinical examinations. Lab tests were performed in all women and included the detection of the concentrations of prolactin, thyroid-stimulating hormone, thyroxine, triiodothyronine, cortisol, gonadotrophic hormones, testosterone, and estradiol by ELISA method.&#x0D; &#x0D; Results: The study results demonstrated that subfertile women with HP are characterized by an increase of follicle-stimulating hormone and free triiodothyronine and a decrease of estradiol and cortisol when compared with fertile patients with HP and Healthy patients.&#x0D; Conclusion: The better glucocorticoid and ovarian function of fertile women with HP supposed to be an essential issue in their reproductive ability.

MON-282 Treatment of Hyperprolactinemia with Ropinirole: An Open-Label Dose Escalation Study

PurposeTreatment of hyperprolactinemia and prolactinomas with ergoline dopamine agonists (DAs) can be complicated by intolerance and resistance. Ropinirole (ROP) is a low cost selective D2/D3 receptor non-ergot DA, approved for treatment of Parkinson’s disease and Restless Leg Syndrome, that has been shown to acutely lower prolactin levels (PRL). This study investigated the efficacy and tolerability of long-term ROP therapy in patients with hyperprolactinemia.Methods & ResultsTen healthy women (21-45 yrs) with hyperprolactinemia were treated with ROP (0.25-6.0mg/d) for 6 months in an open-label dose escalation study. Clinical and biochemical status was assessed monthly and ROP doses were up-titrated to achieve normal PRL levels, restore menses, and eliminate galactorrhea. Two subjects had macroprolactinomas, 7 had microprolactinomas, and 1 had idiopathic hyperprolactinemia. 8/10 had previously been treated with cabergoline and/or bromocriptine. 5/10 were intolerant and 1/10 was resistant to ergot DAs. Pituitary MRIs were performed at baseline and 6 months.ROP was initiated at 0.25mg QHS in 9/10 subjects. One subject with severe DA intolerance was initiated on 0.125mg QHS. Subjects reaching a total daily dose (TDD) > 2.0mg/d were transitioned to ROP extended release. At study completion, TDDs ranged from 1-6mg/d, with a median TDD of 2mg/d. Baseline PRL levels were 136 ± 49ng/ml (1.9-25ng/ml). Stable PRL normalization was achieved in 50% of subjects. Of the subjects achieving normal PRL, 4 had microadenomas and 1 had idiopathic hyperprolactinemia, and the median effective TDD was 1mg/d (1-4mg/d, range). Among those not achieving PRL normalization, PRL decreased 46 ± 5.4% (Mean ± SEM) from baseline, at a median TDD of 4.0mg/d (2-6mg/d, range). In the subject with documented resistance to ergot DAs, PRL decreased from 529 to 320ng/ml, after 3 months of ROP on the maximum dose studied (6mg/d), but rose to 690ng/ml at 6 months. During ROP treatment, menses normalized in 57%, and galactorrhea resolved in 67% of affected subjects. At study completion, tumor size was unchanged in 7/8 prolactinomas. A 20% decrease in tumor size was observed in one macroadenoma, accompanied by a 30% reduction in PRL levels. There were no changes in BP, HR, weight, renal or kidney function. Mild adverse effects (AEs) were recorded in 80% of subjects. Fatigue (60%), nausea (40%), and headache (20%) were most common. Reported AEs declined after month 1 and ROP was not discontinued due to intolerance.ConclusionThese data provide support for the efficacy of ROP in the treatment of hyperprolactinemia in patients with microprolactinomas and idiopathic hyperprolactinemia. While further study is needed, ROP treatment for hyperprolactinemia could be considered in patients with ergot DA intolerance or significant cardiac valve disease.

Macroprolactinemia in patients with hyperprolactinemia: an experience from a single tertiary center.

Macroprolactinemia frequently causes misdiagnosis, unnecessary investigation and inappropriate treatment in hyperprolactinemic patients. Aim of this study is to investigate the prevalence and clinical characteristics of Thai patients with macroprolactinemia. We performed a cross-sectional study in 56 hyperprolactinemic patients (51 women and 5 men) whose sera were subsequently tested for the presence of macroprolactin. Recovery of less than 40% of serum prolactin after polyethylene glycol (PEG) precipitation was indicative of macroprolactinemia. Our study revealed 19.64% (11/56) of patients with hyperprolactinemia were found to have a preponderance of macroprolactin. All patients with macroprolactinemia were women, of which eight of them were initially diagnosed as idiopathic hyperprolactinemia and mistreated with dopamine agonist medications. Interestingly, neuroradiological abnormalities were reported in three patients with macroprolactinemia, 2 cases with prolactinoma and one case with stalk effect hyperprolactinemia. In conclusion, nearly one-fifth of our patients with hyperprolactinemia have macroprolactinemia. This finding suggests that the diagnostic algorithm of all patients with hyperprolactinemia should include the PEG precipitation test as the initial step.Domain: Endocrinology

Serum prolactin binding in various forms of hyperprolactinemia

Binding of 125I-labeled prolactin in the sera of women with different forms of hyperprolactinemia was studied. Antiprolactin autoantibodies were detected in the blood of 24% of women with idiopathic hyperprolactinemia. In contrast to idiopathic hyperprolactinemia, there were no autoantibodies to prolactin in pregnant women with physiological hyperprolactinemia and in hyperprolactinemia of tumor origin. These data indicate that the presence of these antibodies in circulating blood can be one cause of idiopathic hyperprolactinemia. Moreover, the prevalence of high-molecular form of immunoreactive prolactin in the blood can be due to binding of an appreciable amount of prolactin monomer to antiprolactin autoantibodies.

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

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

Aetiologies of Hyperprolactinaemia: A retrospective analysis from a tertiary healthcare centre.

ObjectivesThis study aimed to evaluate the aetiologies of hyperprolactinaemia in the United Arab Emirates (UAE).MethodsThis retrospective study used laboratory databases to identify all patients who underwent evaluation for prolactin at Tawam Hospital, Al Ain, UAE, between 2009 and 2015. Of those 2,280 patients, all patients with low or normal prolactin (n = 1,315) were excluded. Subsequently, charts of the remaining patients (n = 965) with hyperprolactinaemia were reviewed and those with incomplete work-ups or insufficient documentation of the hyperprolactinaemia’s aetiology were excluded (n = 458).ResultsA total of 507 patients were included in the study. The average age at prolactin evaluation was 36 ± 13.2 years and the majority (67.1%) of patients were female. The most common reasons for requesting prolactin were menstrual disorders (29.5%), infertility (18%), evaluation of sellar masses (14.3%), ruling out seizures (13.4 %) and monitoring while on psychiatric medications (8.7%). The most common causes of hyperprolactinaemia were prolactinoma (17%), transient hyperprolactinaemia (14.6%), drug-induced side effects (14.4%), polycystic ovarian syndrome (11.8%) and seizure disorder (7.7%). In females, common aetiologies were prolactinomas, transient and idiopathic hyperprolactinaemia, while sellar masses, seizures, chronic kidney disease and acute illnesses were common aetiologies of hyperprolactinaemia in males. The prolactin level varied between the different aetiologies and a level of >250 ng/mL was suggestive of macro-prolactinoma.ConclusionA significant proportion of patients with hyperprolactinaemia have transient hyperprolactinaemia. Before further investigations are carried out, prolactin level assessment should be repeated, especially in patients with mild hyperprolactinaemia.

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

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

Comparative Study of the Effects of Chamomile (Matricaria Chamomilla L.) and Cabergoline on Idiopathic Hyperprolactinemia: A Pilot Randomized Controlled Trial.

Chamomile is a fascinating plant quoted in several traditional medicine texts, which has broad-spectrum pharmacological activity and medicinal uses. The aim of this study was to assess the efficacy of chamomile syrup in reducing serum prolactin in women with idiopathic hyperprolactinemia. The study was a randomized, controlled clinical trial that was conducted on 56 women with idiopathic hyperprolactinemia for a study period of four weeks. Patients were randomly enrolled in two parallel arms and were treated by chamomile syrup at a dose of 5 mL twice daily or cabergoline tablet orally at a dose of 0.25 mg twice weekly. Serum prolactin levels were measured at baseline and the end of the 4-week study period. Any report of adverse events was also recorded. Results revealed that within the cabergoline group the reduction in the mean prolactin level was significantly greater than that of the chamomile group (p <0.0001). It was also found that decline in the mean prolactin level was statistically significant within the chamomile group (p <0.0001). Chamomile syrup seems to be effective on serum prolactin reduction in women with idiopathic hyperprolactinemia. However, studies with a larger sample size and for a longer follow-up period are recommended.