Diagnosis 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)

ABSTRACT Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correct cause of hyperprolactinemia and manage the patient properly. 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 medication-induced hyperprolactinemia in women.

Serum levels of megaprolactin and gonadal hormones in patients with hyperprolactinemia induced by antipsychotics and their clinical significance / 中国基层医药

Objective:To investigate serum levels of macroprolactin and gonadal hormones in patients with hyperprolactinemia induced by antipsychotics and their clinical significance.Methods:A total of 105 female patients with schizophrenia who received treatment in Huzhou Third Municipal Hospital from June 2017 to October 2018 were included in this study. All these patients received the antipsychotic drug clozapine for 2 months. Then 50 patients with hyperprolactinemia were included in the observation group, and 55 patients who had no hyperprolactinemia were included in this control group. The scores of the Scale for the Assessment of Negative Symptoms and Scales for the Assessment of Positive Symptoms were compared between the two groups. Serum levels of macroprolactin, progesterone, testosterone, estradiol, prolactin, luteinizing hormone, and follicle-stimulating hormone were then compared between the two groups. The Spearman correlation analysis was used to analyze the correlation between serum macroprolactin level and serum progesterone, estradiol, prolactin, and luteinizing hormone levels.Results:Serum macroprolactin level in the observation group was significantly higher than that in the control group [(63.80 ± 12.13) ng/mL vs. (59.07 ± 9.84) ng/mL, t = 2.20, P = 0.030). Serum levels of progesterone, testosterone, estradiol, prolactin, luteinizing hormone, and follicle-stimulating hormone were (4.01 ± 0.47) ng/mL, (5.59 ± 1.15) ng/mL, (236.72 ± 15.14) pg/mL, (127.30 ± 12.40) ng/mL, (6.05 ± 1.10) mIU/mL, (8.52 ± 2.13) mIU/mL, respectively, and they were (10.25 ± 1.83) ng/mL, (6.01 ± 1.20) ng/mL, (433.10 ± 20.90) pg/mL, (50.58 ± 6.22) ng/mL, (7.69 ± 2.36) mIU/mL, (8.48 ± 2.01) mIU/mL, respectively in the control group. Serum levels of progesterone, estradiol, and luteinizing hormone in the observation group were significantly lower than those in the control group, and serum level of prolactin in the observation group was significantly higher than that in the control group ( t = 23.41, 54.66, 4.63, 40.61, all P < 0.05). There were no significant differences in serum levels of testosterone and follicle-stimulating hormone between the two groups ( t = 1.82, 0.09, P = 0.071, 0.921). Spearman correlation analysis results showed that serum macroprolactin level was negatively correlated with serum levels of progesterone and estradiol, and it was positively correlated with serum levels of prolactin and luteinizing hormone ( r = -0.42, -0.51, -0.68, 0.70, all P < 0.05). Conclusion:Serum levels of macroprolactin and prolactin were higher, and serum levels of progesterone, estradiol, and luteinizing hormone levels were lower in patients with hyperprolactinemia induced by antipsychotics than in patients without hyperprolactinemia. Serum levels of macroprolactin, prolactin, luteinizing hormone, progesterone, and estradiol were remarkably correlated with the balance of gonadal hormones. The study outcomes are of great innovation and science.

Características clínicas y manejo de la macroprolactinemia como causa de hiperprolactinemia / Clinical characteristics and management of macroprolactinemia as cause of hyperprolactinemia

La macroprolactinemia se define como la presencia de cantidades elevadas de esta isoforma de la prolactina en suero, en conjunto con concentraciones normales de prolactina monomérica. Se trata de una entidad bastante común, considerada entre las tres primeras causas de hiperprolactinemia. Su origen parece responder a mecanismos autoinmunes y el seguimiento de los pacientes afectos durante periodos de 10 años ha demostrado que es una condición crónica. La prueba de elección para el diagnóstico es la cromatografía líquida en columna de gel, pero este es un método costoso que generalmente es suplido por la prueba de precipitación con polietinglicol. Por mucho tiempo ha prevalecido el concepto de que estos pacientes son esencialmente asintomáticos, pero reportes recientes señalan la presencia de síntomas de hiperprolactinemia como parte significativa del cuadro, aunque la literatura actual muestra criterios divergentes. En estos pacientes la realización de resonancia magnética nuclear hipofisaria parece ser un procedimiento innecesario, basado en la escasa frecuencia de resultados positivos. El tratamiento farmacológico con agonistas dopaminérgicos muestran respuestas contradictorias en cuanto a la desaparición de los síntomas y la normalización de los niveles de prolactina. Por tanto, la inexistencia de un consenso en la literatura científica en lo referente a las manifestaciones clínicas y el manejo, obliga a una conveniente valoración individual de cada caso(AU)

Macroprolactinemia is defined as the presence of high quantities of this prolactin isoform in serum, together with normal concentrations of monomeric prolactin. It is a common entity, considered among the three first causes of hyperprolactinaemia. The origin seems to respond to autoimmune mechanisms and the affected patients follow-up during ten years periods has shown that it is a chronic condition. The standard gold test to the diagnostic is gel-filtration chromatography, but it is an expensive method that is generally supplied by the polyethylene glycol precipitation test. During a long time, the concept that these patients are essentially asymptomatic has prevailed, but recent reports stamps the presence of hyperprolactinemia symptoms as a significant part of the entity, although current literature shows divergent criteria. In these patients, performing pituitary magnetic resonance seems to be an unnecessary procedure, based on the rare frequency of positive results. Pharmacological treatment with dopamine agonists shows contradictory responses with regard to symptoms disappearance and prolactin levels normalization. Therefore, the lack of consensus in the scientific literature with regard to the clinical manifestations and the management, requires a convenient individual assessment of each case(AU)

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

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

Importance of screening for macroprolactin in all hyperprolactinaemic sera

Introduction: Prolactin (PRL) exists in different forms in human serum. The predominant form is monomeric PRL (molecular mass 23 kDa) with smaller amounts of big PRL (molecular mass 50–60 kDa) and at times macroprolactin (molecular mass 150–170 kDa). Macroprolactin, generally considered to be biologically inactive, accounts for the major part of prolactin in some patients. Different immunoassays for prolactin differ in reactivity with this macromolecular complex. Aim: The present study was undertaken to assess the incidence of macroprolactinaemia in our cohort of hyperprolactinemic patients. Method: 204 samples with hyperprolactinemia were evaluated for macroprolactinemia by polyethylene glycol (PEG) precipitation and gel fi ltration chromatography (GFC). Recoveries 40% but 50%. The incidence of macroprolactinemia in our cohort of hyperprolactinaemic patients was noted to be 4.4%. Conclusion: Macroprolactin is a signifi cant cause of misdiagnosis, unnecessary investigation, and inappropriate treatment and hence it is useful to screen all patients with high PRL levels with PEG precipitation and to apply GFC to samples with recoveries <50%.