BACKGROUND: Several retrospective and cross-sectional studies have revealed a higher prevalence of autoimmune thyroid diseases (AITD) with a predominance of autoimmune hypothyroidism in prolactinoma patients compared to the general population. To date, we have no data on the clinical course of AITD in these patients. The aim of this prospective study was to assess the clinical course of AITD in female patients with prolactinomas compared to an age- and thyroid-risk factors-matched control group.
METHODS: The study population consisted of 144 females (71 patients/73 controls) who underwent approximately a 6-year follow-up. Physical examination, thyroid ultrasound and laboratory testing (measurement of antibodies to thyroglobulin, thyroid peroxidase, TSH-receptor; serum TSH and FT4 levels) were performed twice - at the baseline and at the follow-up visits.
RESULTS: AITD were diagnosed in 26.8% (n=19) of the patients and 9.6% (n=7) of the controls (p=0.007) at baseline visit. At the end of the follow-up (FU), these percentages increased to 33.8% (n=24) among the patients versus 12.3% (n=9) in the control group (p=0.002). Hypothyroidism was significantly more frequent in prolactinoma patients than in controls at the end of the study (19.7% vs. 4.1%; p=0.003). Two prolactinoma patients had hyperthyroidism at the baseline visit and restored euthyroid state with negative TSH-receptor antibodies during the follow-up. We did not observe hyperthyroidism in the control group. Among the hypothyroid subsets, the average daily levothyroxine dose at FU visit varied from 25 to 200mcg in the prolactinoma group compared to 25 to 50mcg in the control group.
CONCLUSIONS: Female patients with prolactinomas seem to be prone to autoimmune hypothyroidism. As a pathogenetic mechanism, we could suggest the selective immunomodulatory action of PRL predominantly on cell autoimmunity, complement activation and antibody-dependent cytotoxicity, resulting in earlier and more rapid progression of Hashimoto\'s thyroiditis towards hypothyroid state in genetically predisposed individuals.

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

Cryopreservation has destructive effects on the function and structure of spermatozoa. It is known that leptin and prolactin play an active role in decreasing the rates of reactive oxygen species and DNA fragmentation, as well as enhancing sperm motility. Hence, this experiment aimed to investigate the effects of leptin and prolactin as pro-survival factors on the normozoospermic human semen samples during cryopreservation.
Semen samples were collected from 15 healthy, fertile men ranging from 25 to 40 years. Cryopreservation of the samples was performed in liquid nitrogen over a period of two weeks, using five varying concentrations of leptin/prolactin, 0, 10, 100, 500, and 1000ng/ml respectively. Sperm motility, total caspase activity, and mitochondrial and cytosolic ROS were measured by flowcytometry, TUNEL, and other appropriate tests after thawing of the samples.
Both hormones were observed to have positive effects on the motility of the samples post-cryopreservation, the highest improvement being in the 100ng/ml concentration leptin and prolactin in comparison to the control group (P=0.01 and P=0.041, respectively). A significant reduction of mitochondrial ROS was also observed in 100 and 1000ng/ml of leptin (P=0.042), and there was a considerable decrease in the cytosolic ROS in the 100ng/ml of prolactin in comparison to the control group (P=0.048). Total caspase activity was also highly reduced in the 100, 500, and 1000ng/ml of leptin compared to the control group (P=0.039). Interestingly, both hormones also significantly decreased DNA fragmentation in 1000ng/ml compared to the control group (P=0.042).
It can be concluded that leptin and prolactin act as protective agents against cryodamage to spermatozoa during cryopreservation.

Takotsubo syndrome (TTS) is currently described as an acute and usually reversible form of systolic dysfunction of the left ventricle, which more frequently affects postmenopausal women after a stressful emotional event. Although TTS is a rare condition in premenopausal women, in recent years, the number of reported cases has increased. This manuscript reports the first case of a TTS several months after delivery in a 22-year-old woman during lactation. It may also emphasize the role of estrogens in the disease pathogenesis.

BACKGROUND: Low prolactin levels have been found to impair libido and arousal, as well as to reduce wellbeing in young women.
OBJECTIVE: The aim of this study was to investigate whether drug-induced hypoprolactinaemia affects male sexual function and depressive symptoms.
METHODS: 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 were <3ng/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).
RESULTS: 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.
CONCLUSIONS: 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.

Prolactin measurement is very common in standard clinical practice. It is indicated not only in the study of pituitary adenomas, but also when there are problems with fertility, decreased libido, or menstrual disorders, among other problems. Inadequate interpretation of prolactin levels without contextualizing the laboratory results with the clinical, pharmacological, and gynecological/urological history of patients leads to erroneous diagnoses and, thus, to poorly based studies and treatments. Macroprolactinemia, defined as hyperprolactinemia due to excess macroprolactin (an isoform of a greater molecular weight than prolactin but with less biological activity), is one of the main causes of such erroneous diagnoses, resulting in poor patient management when not recognized. There is no unanimous agreement as to when macroprolactin screening is required in patients with hyperprolactinemia. At some institutions, macroprolactin testing by polyethylene glycol (PEG) precipitation is routinely performed in all patients with hyperprolactinemia, while others use a clinically based approach. There is also no consensus on how to express the results of prolactin/macroprolactin levels after PEG, which in some cases may lead to an erroneous interpretation of the results. The objectives of this study were: 1. To establish the strategy for macroprolactin screening by serum precipitation with PEG in patients with hyperprolactinemia: universal screening versus a strategy guided by the alert generated by the clinician based on the absence or presence of clinical symptoms or by the laboratory when hyperprolactinemia is detected. 2. To create a consensus document that standardizes the reporting of prolactin results after precipitation with PEG to minimize errors in the interpretation of the results, in line with international standards.

BACKGROUND: Low prolactin levels have been found to impair libido and arousal, as well as to reduce wellbeing in young women.
OBJECTIVE: The aim of this study was to investigate whether drug-induced hypoprolactinaemia affects male sexual function and depressive symptoms.
METHODS: 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 were <3ng/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).
RESULTS: 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.
CONCLUSIONS: 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.

BACKGROUND: Prolactin (PRL) binds its receptor (PRLR) and stimulates cell proliferation, differentiation and survival in prostate cancer (PCa) cell lines via STAT5a, MAPK and AKT.
OBJECTIVE: To evaluate the expression of PRL and PRLR in normal and tumor prostate tissues with different Gleason patterns.
METHODS: Samples of normal, benign prostatic hyperplasia and PCa with different Gleason patterns were selected from radical prostatectomy. The intensity, location and percentage of stained cells for PRL and PRLR were evaluated by Immunohistochemistry. Co-localization was observed by confocal microscopy.
RESULTS: PRL was expressed diffusely and with a mild intensity in the cytoplasm of normal and tumor prostate luminal cells. Its expression only augmented in the Gleason 3 pattern (p< 0.0001). The immunostaining intensity and the percentage of positive cells for PRLR did not vary between normal and tumor tissues. However, the location of the PRLR was modified by the tumorigenic process.In non-tumor tissues, PRLR expression was mostly in plasma membrane in the apical zone of epithelial cells. In tumor tissues, it was expressed in intracellular vesicles.The co-localization of PRL and PRLR was demonstrated in normal and tumor tissues suggesting that PRL could be acting in an autocrine and paracrine manner.
CONCLUSIONS: PRL and its receptor were present in the cytoplasm of the epithelial cells of the normal and tumor prostate gland. In tumor tissues, the change in the location and appearance of cryptic PRLRs that store PRL may keep active the different signaling pathways related to cell proliferation and survival.
INTRODUCCIÓN: La prolactina (PRL) se une a su receptor (PRLR) y estimula la proliferación celular, la diferenciación y la supervivencia de la líneas celulares de cáncer de próstata vía STAT5a, MAPK y AKT.OBJETIVO: Evaluar la expresión de la PRL y PRLR en tejido normal y tejido de cáncer de próstata con varios patrones de Gleason.MÉTODOS: Se seleccionaron muestras de tejido benigno, hiperplasia y cáncer de próstata con diferentes patrones de Gleason de prostatectomías radicales. La intensidad, localización y porcentaje de células teñidas por PRL y PRLR fueron evaluadas por immunohistoquimica. La co-localización se observó con microscopio confocal.RESULTADOS: PRL se presentó de forma difusa y con intensidad media en el citoplasma de células luminales normales y de tumor prostático. La expresión solamente aumentó en patrón Gleason 3 (p<0,0001). La intensidad de la tinción immunohistoquímica y el porcentaje de células positivas para PRLR no varió entre células normales y tejidos tumorales. Pero, la localización del PRLR fue modificada por el proceso generador del tumor. En tejidos no-tumorales, la expresión de PRLR fue sobre todo en la membrana plasmática en la zona apical de las células epiteliales. En tejidos tumorales, se presentó en las vesículas intracelulares. La co-localizacion de la PRL y PRLR se demostró en tejido normal y tumoral sugeriendo que la PRL funciona con un efecto autocrino y paracrino.CONCLUSIÓN: La PRL y su receptor estuvieron presentes en el citoplasma de células epiteliales de tejido normal y glándula prostática tumoral. En tejidos tumorales, el cambio de localización y la apariencia cripticas del PRLR que guarda la PRL debe mantener activos los diferentes caminos de señalización relacionados con la proliferación celular y la supervivencia.

Prolactin measurement is very common in standard clinical practice. It is indicated not only in the study of pituitary adenomas, but also when there are problems with fertility, decreased libido, or menstrual disorders, among other problems. Inadequate interpretation of prolactin levels without contextualizing the laboratory results with the clinical, pharmacological, and gynecological/urological history of patients leads to erroneous diagnoses and, thus, to poorly based studies and treatments. Macroprolactinemia, defined as hyperprolactinemia due to excess macroprolactin (an isoform of a greater molecular weight than prolactin but with less biological activity), is one of the main causes of such erroneous diagnoses, resulting in poor patient management when not recognized. There is no unanimous agreement as to when macroprolactin screening is required in patients with hyperprolactinemia. At some institutions, macroprolactin testing by polyethylene glycol (PEG) precipitation is routinely performed in all patients with hyperprolactinemia, while others use a clinically based approach. There is also no consensus on how to express the results of prolactin/macroprolactin levels after PEG, which in some cases may lead to an erroneous interpretation of the results. The objectives of this study were: 1. To establish the strategy for macroprolactin screening by serum precipitation with PEG in patients with hyperprolactinemia: universal screening versus a strategy guided by the alert generated by the clinician based on the absence or presence of clinical symptoms or by the laboratory when hyperprolactinemia is detected. 2. To create a consensus document that standardizes the reporting of prolactin results after precipitation with PEG to minimize errors in the interpretation of the results, in line with international standards.