Atypical pituitary hormone-target tissue axis / 医学前沿

A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an "atypical pituitary hormone-target tissue axis." This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the "atypical pituitary hormone-target tissue axis" could enable the identification of novel therapeutic targets for metabolic diseases.

Establishment and comparison of two methods to produce a rat model of mammary gland hyperplasia with hyperprolactinemia

Abstract This study aimed to establish and compare models of mammary gland hyperplasia (MGH) with hyperprolactinemia (HPRL) using two different methods. The models provide information on the relationship between mammary gland hyperplasia and associated hormones. Model A was constructed using intramuscular injections of estradiol benzoate injection (EBI), followed by progesterone (P), and then metoclopramide dihydrochloride (MDI). Model B was designed by administering MDI, follow by EBI, and then P intramuscularly. Model B showed higher MGH progression compared with model A. Notably, increase in estradiol (E2) was negatively correlated with prolactin (PRL) secretion. However, PRL levels in model B were significantly higher compared with the levels in model A. Estrogen (ER), prolactin receptor (PRLR), and progesterone receptor (PR) mRNA and protein expression levels in model B rats were positively correlated with changes in the corresponding hormone levels. However, E2, P, and PRL levels in model A showed no direct relationship with levels of the mRNAs of related hormones and protein expression levels. Our results suggest that model B is an appropriate model of MGH with HPRL that can be used to perform further studies about the interactions of the E2, P, and PRL hormones in this disorder.

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases / 北京大学学报(医学版)

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.

Manejo preoperatorio de los adenomas hipofisarios. Lo que un residente de neurocirugía debe conocer / Preoperative management of pituitary adenomas. What a neurosurgery resident should know

Las lesiones selares son una patología con una incidencia de 3,2 a 4 / 100,000 y una prevalencia de 78 a 94 / 100,000. Un 10% son incidentalomas en la población adulta. Se cree que su prevalencia en el orden mundial actualmente va en aumento.En relación a las manifestaciones clínicas, cabe destacar que es una de las pocas enfermedades que pueden manifestarse tanto por signos y síntomas neurológicos (por ejemplo: hemianopsia bitemporal, síndrome de hipertensión endocraneana debido a hidrocefalia, entre otros), como también por síndromes endocrinológicos (por ejemplo: síndrome de Cushing, acromegalia, amenorrea-galactorrea, infertilidad).Todo paciente debe presentar un estudio clínico-radiológico completo, lo que permitirá un correcto diagnóstico y categorización del mismo.El objetivo del presente trabajo es proporcionar al neurocirujano en formación los conceptos claves que servirán de sustento para el manejo preoperatorio de un paciente con adenoma hipofisario.

Sellar lesions are a pathology with an incidence of 3.2 to 4 / 100.000 and a prevalence of 78 to 94 / 100.000. Normally, 10% of them are incidentalomas and adult patients are in the highest risk group. Because it ́s prevalence in the world is currently increasing, it is of extremely importance to study and understand this pathology. In relation to the clinical manifestations, it should be noted that it is one of the few diseases that can manifest through neurological signs and symptoms like bitemporal hemianopsia, endocranial hypertension syndrome due to hydrocephalus, as well as endocrinological syndromes like Cushing's, acromegaly, amenorrhea-galactorrhea and infertility. One of the most important things to notice is that the treatment success in this pathology comes with the correct diagnosis and characterization of it, for what all patients should have a complete clinical-radiological evaluation.In this study, we establish a guide with concepts and key tools to support the medical personal during a pre-surgical preparation of patients with pituitary adenoma.

Lacrimal gland atrophy and dry eye related to isotretinoin, androgen, and prolactin: differential diagnosis for Sjögren's syndrome / Atrofia das glândulas lacrimais e olho seco relacionados aisotretinoína, androgênio e prolactina: diagnóstico diferencial com a síndrome de Sjögren

ABSTRACT This report is of three cases of sicca syndrome, initially suspected to be Sjögren's syndrome, which was ruled out by clinical and laboratory investigations. The patients were a 24-year-old woman, a 32-year-old man, and a 77-year-old woman with chronic symptoms of sicca syndrome, including dry eye syndrome. The first case was associated with the use of isotretinoin, a retinoic acid. The second was associated with the use of anabolic androgenic steroids, and the third was related to a prolactin- secreting pituitary adenoma. All cases manifested sicca, including dry eye syndrome, after those events, and the manifestations persisted. Magnetic resonance imaging revealed bilateral atrophy of the lacrimal gland. The medical history, ocular examinations, laboratory exams, and magnetic resonance images confirmed dry eye syndrome; however, the exams were all negative for Sjögren's syndrome. The lacrimal gland was absent on magnetic resonance imaging in all three cases. The clinical history revealed that the signs and symptoms appeared after chronic exposure to retinoic acid, anabolic androgenic steroids, and a prolactin-secreting pituitary adenoma, respectively. Chronic isotretinoin, anabolic androgenic steroids, and prolactin-secreting pituitary adenoma or, in this last case, its inhibitory treatment, can cause lacrimal gland atrophy, sicca syndrome, and dry eye syndrome, and a differential diagnosis of Sjögren's syndrome. Further studies on doses, time, and other susceptibilities to the long-lasting adverse effects of retinoic acid, anabolic androgenic steroids, and the repercussions of prolactin-secreting pituitary adenoma are necessary to confirm and expand upon these associations.

RESUMO O relato descreve três casos de síndrome de sicca, inicialmente suspeitos de serem a síndrome de Sjögren, que fo­ram negados pela investigação clínica e laboratorial. O primeiro associado ao uso de isotretinoína, um ácido retinóico, o segundo ao uso de esteroides androgênicos anabolizantes e o terceiro relacionado ao adenoma da hipófise secretora da prolactina, todos manifestaram sicca, incluindo a síndrome do olho seco após esses eventos e as manifestações persistem. A ressonância magnética revelou atrofia bilateral da glândula lacrimal. Eles eram uma mulher de 24 anos, um homem de 32 anos e uma mulher de 77 anos com sintomas crônicos da síndrome de sicca, incluindo a síndrome do olho seco. A história médica, o exame ocular, os exames laboratoriais e a ressonância magnética foram confirmados como síndrome do olho seco, no entanto, todos os exames foram negativos para a síndrome de Sjögren. A glândula lacrimal estava ausente na ressonância magnética nos três casos. A história clínica revelou que sinais e sintomas se manifestaram após exposição crônica ao ácido retinóico, esteróides anabolizantes androgênicos e adenoma secretivo da prolactina hipofisária, respectivamente. Isotretinoína crônica, esteroides anabólicos androgênicos e adenoma hipofisário secretor de prolactina ou, neste último caso, seu tratamento inibitório pode ser a causa da atrofia da glândula lacrimal, síndrome da sicca e síndrome do olho seco e diagnóstico diferencial da síndrome de Sjögren. Estudos adicionais sobre doses, duração e outras suscetibilidades aos efeitos adversos duradouros do ácido retinóico, esteroides androgênicos anabólicos e repercussões do adenoma da hipófise secretora da prolactina são necessários para confirmar e detalhar essas associações.

Hiperprolactinemia e infertilidad / Hyperprolactinemia and infertility

La prolactina es una hormona hipofisiaria implicada en diversas funciones tales como reproductivas, lactancia y metabólicas. El hallazgo de hiperprolactinemia es frecuente en mujeres que consultan por infertilidad, oscilando entre el 15 y el 20%. Sus manifestaciones clínicas incluyen trastornos del ciclo, galactorrea, infertilidad y osteoporosis. Cuando hay tumores que superan 1 cm de diámetro pueden asociarse a alteraciones visuales. Aunque la hiperprolactinemia puede ser producida por el embarazo, el consumo de algunos fármacos, los trastornos tiroideos, las alteraciones hepáticas y renales, su causa más frecuente es la presencia de adenomas hipofisiarios productores de prolactina. Pueden ser microadenomas cuando su tamaño es menor de 10 mm y que representan el 90% o macroadenomas cuando son de mayor tamaño. La prolactina se encuentra bajo un estrecho control de su secreción a través de un sistema de retroalimentación de asa corta que hace que se libere dopamina que frena su producción. También se han descrito péptidos liberados de prolactina entre los que se encuentra la TRH. El exceso en su producción inhibe directamente la pulsatilidad de la GnRH y disminución en los pulsos de LH. Este cambio conduce a ciclos anovulatorios. Para su manejo se encuentran aprobados en Colombia fármacos agonistas de la dopamina como bromocriptina y cabergolina, siendo este último más efectivo. El manejo con cirugía transesfenoidal se reserva para aquellos casos en los que el tratamiento farmacológico ha fallado.

Prolactin is an hypophyseal hormone implicated in various functions such as reproductive, lactation and metabolic. Finding hyperprolactinemia is frequent in women consulting for infertility, ranging between 15 and 20%. Its clinical manifestations include menstrual cycle irregularities, galactorrhea, infertility and osteoporosis. When tumors greater than 1 cm in diameter are present visual disturbances may appear. Although hyperprolactinemia may be produced by pregnancy, certain medications, thyroid disfunction, hepatic or renal disfunction, the most frequent cause is the presence of prolactin secreting adenomas. They can be micro adenomas when their diameter is less than 10 mm, representing 90% or macro adenomas when their size is greater. Prolactin secretion is under a close control through a short loop feedback system, that makes dopamine to be secreted which lowers its production. Releasing peptides have been described, including TRH. Excess in its production directly inhibits GnRH pulsatility lowering LH pulses. This change conducts to anovulatory cicles, For its treatment in Colombia dopamine agonists have been approved, including bromocriptine and cabergoline, the last one being mor effective. Surgical management with transesphenoidal approach is reserved for those cases in which pharmacological treatment has failed.

Semen parameters in men recovered from COVID-19 / 亚洲男科学杂志(英文版)

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.

Prolactin level and breastmilk production among mothers of low-birth-weight Infants admitted to level II Neonatal Intensive Care Unit

Background@#Kangaroo mother care (KMC) has been proven by several studies to promote breastfeeding, but many of the studies focus on the success of exclusive breastfeeding, and less on its galactogenic effects. @*Objective@#We aim to determine the maternal serum prolactin levels and breastmilk volume of mothers who rendered KMC to their infants. @*Materials and Methods@#This is a randomized controlled, open-labeled, interventional study in the Neonatal Intensive Care Unit of a tertiary government hospital. Infants weighing < 2000 grams admitted in NICU Level II, together with medically stable mothers and no contraindication for breastfeeding were simultaneously enrolled. Primary outcome measures were maternal serum prolactin levels and expressed milk volume on day 3 and day 7 postpartum. Two-sample t-test was used to compare groups, and paired t-test to compare within groups. Tests were two-tailed, with a p-value of < 0.05 considered statistically significant. @*Trial Registration@#Australia-New Zealand Clinical Trial Registry ID ACTRN12614000218695 @*Results@#Fifty mother-infant dyads were equally allocated into KMC and control groups (p < 0.001). There was significantly larger milk volume on the third day (29.6 ± 27.8 mL vs 16.3 ± 26.1 mL; p < 0.001) and seventh post-partum day (72.4 ± 62.3 mL vs 47.3 ± 43.8 mL; p < 0.000). There were increased serum prolactin levels compatible with post-partum state. The increase was more evident in the KMC (5244 ± 2702 mIU/L, on the 3rd postpartum day versus 4969 ± 2426 mIU/L, on the 7th postpartum day, p = 0.996) compared to control group (4129 ± 2485 mIU/L on the 3rd postpartum day versus 3705 ± 2731 mIU/L on the 7th postpartum day, p = 0.301). @*Conclusion@#We noted a significantly larger milk volume in the KMC group. There was also a greater increase in the prolactin levels in the KMC group, but this did not reach statistical significance. Further studies should be done to determine mechanism of galactogenesis through KMC.

Identification and sequence analysis of prolactin receptor and its differential expression profile at various developmental stages in striped hamsters

Prolactin (PRL) plays critical roles in regulation of biological functions with the binding of specific prolactin receptor (PRLR). Revealing the expression patterns of PRLR at different developmental stages is beneficial to better understand the role of PRL and its mechanism of action in striped hamsters. In this study, the cDNA sequence of PRLR (2866-base-pairs) was harvested from the pituitary of mature female striped hamsters (Cricetulus barabensis) that contains an 834-base-pair 5′-untranslated region (1-834 bp), a 1848-base-pair open reading frame (835-2682 bp), and a 184-base-pair 3′-untranslated region (2683-2866). The 1848-base-pair open reading frame encodes a mature prolactin-binding protein of 592 amino acids. In the mature PRLR, two prolactin-binding motifs, 12 cysteines, and five potential Asn-linked glycosylation sites were detected. Our results showed that the PRLR mRNA quantity in the hypothalamus, pituitary, ovaries, or testis was developmental-stage-dependent, with the highest level at sub-adult stage and the lowest level at old stage. We also found that PRLR mRNAs were highest in pituitary, medium level in hypothalamus, and lowest in ovaries or testis. PRLR mRNAs were significantly higher in males than in females, except in the hypothalamus and pituitary from 7-week-old striped hamsters. Moreover, the PRLR mRNAs in the hypothalamus, pituitary, and ovaries or testis were positively correlated with the expression levels of GnRH in the hypothalamus. These results indicated that the PRLR has conserved domain in striped hamster, but also possesses specific character. PRLR has multiple biological functions including positively regulating reproduction in the striped hamster.

Panhipopituitarismo secundario a hemorragia obstétrica profusa / Panhypopituitarism secondary to profuse obstetric haemorrhage

El síndrome de Sheehan o necrosis hipofisaria posparto, constituye la causa más importante de panhipopituitarismo, que de forma ocasional se asocia a hemorragia obstétrica profusa asociada a choque hipovolémico hemorrágico, ocasionando un colapso circulatorio intenso debido a isquemia de la adenohipófisis durante el parto o después del mismo, debido a que esta glándula endócrina sufre importantes cambios anatómicos e histológicos durante el embarazo, los cuales incrementan su volumen hasta en 40%. De esta forma, se produce una secreción reducida de las hormonas que ayudan a regular el crecimiento, la reproducción y el metabolismo, evidenciando en el examen hormonal detallado insuficiencia específicamente de la hormona de crecimiento, foliculoestimulante, luteinizante, estimulante de tiroides, adrenocorticotropica y prolactina predisponiendo a la paciente a inestabilidad hemodinámica a corto plazo así como desequilibrio hormonal permanente. Por esta importancia, es que se presenta el caso de una paciente que ingresó a la Unidad de Terapia Intensiva tras cesárea iterativa debido a acretismo placentario llegando a la histerectomía total intercurriendo con choque hemorrágico, quien cursó durante su estancia en la Unidad con ausencia de recuperación neurológica total y características propias de síndrome de Sheehan, confirmándose el mismo por los niveles hormonales bajos y la ausencia de imagen en la silla turca correspondiente a la necrosis hipofisaria evidenciado por resonancia magnética, realizándose además una sucinta revisión acerca de la literatura relacionada actual.

ABSTRACT Sheehan syndrome or postpartum pituitary necrosis is the most common cause of hypopituitarism and occurs secondary to profuse obstetric haemorrhage with subsequent hypovolemic hemorrhagic shock, with intense circulatory collapse, predisposing to pituitary ischemia during delivery or after the same, due to the hypertrophic changes that occur in this gland during pregnancy. In this syndrome exists a reduced secretion of the hormones that regulate growth, reproduction and metabolism. We present the case of a female patient admitted to the Critical Care Unit after iterative cesarean due to placenta accreta and total hysterectomy, in hypovolemic shock secondary to severe hemorrhage, being suspicious of Sheehan´s syndrome, with characteristic clinical features, low hormone levels and the absence of image in the Turkish chair corresponding to the pituitary necrosis.

Hyperprolactinemia associated with psychiatric disorders / Hiperprolactinemia asociada con trastornos psiquiátricos

Abstract Hyperprolactinemia may be associated with psychiatric disorders in the context of two scenarios: antipsychotic-induced hyperprolactinemia and psychiatric disorders arising from the medical treatment of hyperprolactinemia. Both situations are particularly common in psychiatric and endocrine clinical practice, albeit generally underestimated or unrecognized. The aim of this article is to provide tools for the diagnosis and treatment of hyperprolactinemia associated with psychiatric disorders to raise awareness, especially among psychiatrists and endocrinologists, so that these professionals can jointly focus on the appropriate management of this clinical entity.

Resumen La hiperprolactinemia puede asociarse con trastornos psiquiátricos en el contexto de dos escenarios: la hiperprolactinemia inducida por antipsicóticos y trastornos psiquiátricos surgidos por el tratamiento médico de la hiperprolactinemia. Ambas situaciones son particularmente comunes en la práctica clínica psiquiátrica y endocrinológica, aunque generalmente subestimadas o inadvertidas. El objetivo de este artículo es proporcionar herramientas de diagnóstico y tratamiento de la hiperprolactinemia asociada a trastornos psiquiátricos, para concientizar particularmente a psiquiatras y endocrinólogos a enfocar en conjunto el manejo apropiado de esta entidad.

O uso do cloridrato de piridoxina para induzir estro em cadelas / The use of pyridoxine chloridrate to induce estrus in female dogs

Os agonistas dopaminérgicos são utilizados para induzir estro em cadelas, pois atuam na síntese e liberação de prolactina. Objetivou-se avaliar o efeito da piridoxina como indutor de estro em cadelas por agir na neurotransmissão dopaminérgica. Foram selecionadas 40 cadelas em anestro, divididas em quatro grupos experimentais, tratadas com 10mg/kg/dia (G1) e 50mg/kg/dia (G2) de cloridrato de piridoxina, 5µg/kg/dia (G3) de cabergolina e grupo controle/placebo (G4) por até 20 dias. Foram realizadas citologias vaginais a cada 24h para acompanhamento do ciclo estral e análises hormonais (FSH, LH e PRL) no dia zero e 120h do início do tratamento. As cadelas do G3 (100%) manifestaram proestro após 12 dias de tratamento aproximadamente, tempo inferior aos demais grupos (P<0,05). Apenas uma cadela do G1 e uma do G2 ficaram gestantes contra oito fêmeas do G3 e nenhuma do G4 (P<0,05). As concentrações plasmáticas de prolactina foram reduzidas nas fêmeas do G2 e G3 (P<0,05). As demais avaliações hormonais não sofreram influência do tratamento (P>0,05). O cloridrato de piridoxina foi ineficiente para induzir estro em cadelas, mas foi capaz de suprimir a prolactina, de forma semelhante à cabergolina, quando utilizado na dose de 50mg/kg/dia.(AU)

Dopaminergic agonists are used to induce estrus in female dogs as they act in the synthesis and release of prolactin. The objective of this study was to evaluate the effect of pyridoxine as an inducer of estrus by acting on dopaminergic neurotransmission. A total of 40 female dogs in anestrous were divided into four experimental groups treated with 10mg/kg/day (G1) and 50mg/kg/day (G2) of pyridoxine hydrochloride, 5µg/kg/day (G3) of cabergoline and control group/placebo (G4) for up to 20 days. Vaginal cytologies were performed every 24h for follow-up of the estrous cycle and hormonal analyzes (FSH, LH and PRL) on day zero and 120 hours after the start of treatment. The female dogs from G3 (100%) showed proestrus after 12 days of treatment, less time than the other groups (P< 0.05). Only one female from G1 and one from G2 were pregnant against eight from G3 and none from G4 (P< 0.05). Plasma concentrations of prolactin were reduced by treatment in females from G2 and G3 (P< 0.05). The other hormonal evaluations were not influenced by the treatment (P> 0.05). Pyridoxine chloridrate was inefficient to induce estrus in female dogs but was able to suppress prolactin when used at a dose of 50mg/kg/day.(AU)

Body self-image disturbances in women with prolactinoma

Objective: To evaluate body dissatisfaction and distorted body self-image in women with prolactinoma. Methods: Body dissatisfaction and distorted body self-image were evaluated in 80 women with prolactinoma. All patients were in menacme, 34% had normal body mass index (BMI), and 66% were overweight. Most patients (56.2%) had normal prolactin (PRL) levels and no hyperprolactinemia symptoms (52.5%). The Body Shape Questionnaire (BSQ) was used to assess the patients' dissatisfaction with and concern about their physical form, and the Stunkard Figure Rating Scale (FRS) was used to assess body dissatisfaction and distorted body self-image. The patients were divided according to PRL level (normal vs. elevated) and the presence or absence of prolactinoma symptoms. Results: The normal and elevated PRL groups had similar incidences of body dissatisfaction and distorted body self-image. However, symptomatic patients reported a higher incidence of dissatisfaction than asymptomatic patients. Distorted body self-image was less common among symptomatic patients. Conclusion: Symptomatic patients showed higher body dissatisfaction, but lower body self-image distortion. The presence of symptoms may have been responsible for increased body awareness. The perception of body shape could have triggered feelings of dissatisfaction compared to an ideal lean body. Therefore, a distorted body self-image might not necessarily result in body dissatisfaction in women with prolactinomas.

Resolution of headache after reduction of prolactin levels in hyperprolactinemic patients / Resolução de cefaleia após redução dos níveis de prolactina em pacientes com hiperprolactinemia

Abstract Prolactin (PRL) secreting adenomas are associated with high incidence of headache. The role of hyperprolactinemia in the headache context is not clear, nor is the effect of its treatment on headache. Methods: The present longitudinal study evaluated hyperprolactinemic patients (69), in terms of presence and characteristics of headache before and after hyperprolactinemia treatment. Results: Headache was reported by 45 (65.2%) patients, independent of the etiology of hyperprolactinemia. The migraine phenotype was the most prevalent (66.6%). Medications used in the treatment of headache not changed during the study. The first line of treatment of hyperprolactinemia was dopaminergic agonists. In the last reevaluation, PRL level under treatment was within the reference range in 54.7% of the cases, and it was observed complete or partial resolution of the headache in 75% of the cases. The median PRL at this time in patients with complete headache resolution was 17 ng/mL, in those who reported partial recovery was 21 ng/mL, and in those in whom the headache did not change was 66 ng/mL, with a significant difference between the group with complete headache resolution vs. the group with unchanged headache (p=0.022). In the cases with complete headache resolution, the median fall on PRL levels was 89% and in those cases with partial headache resolution 86%, both significantly different (p<0.001) from the fall in the cases with an unchanged headache. Conclusion: Data allow us to conclude that, in this series, in the majority of cases the reduction in the level of PRL was followe3d by cessation or relief of the pain.

Resumo Os adenomas secretores de prolactina (PRL) estão associados à alta incidência de cefaleia. O papel da hiperprolactinemia no contexto da dor de cabeça não está claro, nem o efeito da redução dos níveis da PRL na cefaleia. Métodos: O presente estudo longitudinal avaliou pacientes hiperprolactinêmicos (69), quanto à presença e às características da cefaleia antes e após o tratamento da hiperprolactinemia. Resultados: Cefaleia foi relatada por 45 (65,2%) pacientes, independente da etiologia da hiperprolactinemia. O fenótipo de enxaqueca foi mais prevalente (66,6%). Os medicamentos usados ​​no tratamento da cefaleia não foram alterados durante o estudo. A primeira linha de tratamento da hiperprolactinemia foram os agonistas dopaminérgicos. Na última reavaliação, o nível de PRL sob tratamento estava dentro da faixa de referência em 54,7% dos casos, observando-se resolução completa ou parcial da cefaleia em 75% dos casos. A mediana de PRL neste momento em pacientes com resolução completa da cefaleia foi de 17 ng/mL, nos que relataram recuperação parcial foi de 21 ng/mL, e naqueles em que a cefaleia não se alterou foi de 66 ng/mL, com uma diferença significativa entre o grupo com resolução completa da cefaleia versus o grupo com cefaleia inalterada (p=0,022). Nos casos com resolução completa da cefaleia, a queda mediana nos níveis de PRL foi de 89% e nos casos com resolução parcial de cefaleia de 86%, ambos significativamente diferentes (p<0,001) da queda nos casos com cefaleia inalterada. Conclusão: Os dados permitem concluir que, nesta série, na maioria dos casos, a redução do nível de PRL foi seguida pela cessação ou alívio da dor.

Quiste de bolsa de Rathke e hiperprolactinemia, una causa infrecuente de amenorrea primaria / Rathke cleft cysts and hyperprolactinemia, an uncommon cause of primary amenorrhea

El quiste de la bolsa de Rathke es una lesión epitelial benigna de la región selar, formada a partir de remanentes embrionarios. La mayoría de los casos son asintomáticos, aunque pudiera presentarse con cefalea, disfunción hipofisaria y trastornos visuales, muy infrecuentemente como apoplejía hipofisaria. Se presenta el caso de una paciente que, habiendo presentado amenorrea primaria, se le realiza el diagnóstico de quiste de la bolsa de Rathke con hiperprolactinemia, logrando menarquia luego del tratamiento con cabergolina.

Rathke's cyst is a benign epithelial lesion of the sellar region, formed from embryonic remnants. Most cases are asymptomatic although it could present with headache, pituitary dysfunction and visual disorders, very infrequently as pituitary stroke. We present the case of a patient who, having presented primary amenorrhea, is diagnosed with Rathke's cyst with hyperprolactinemia, achieving menarche after treatment with cabergoline.

Intelectin-1 and Endocrinological Parameters in Women with Polycystic Ovary Syndrome: Effect of Insulin Resistance / 이화의대지

OBJECTIVES: We aimed to evaluate the effect of insulin resistance (IR) on serum Intelectin-1 and endocrinological hormones levels in obese and non-obese women with and without polycystic ovary syndrome (PCOS) in Basrah, Iraq.METHODS: From 124 women volunteers, 60 patients with primary and 64 patients with secondary, while 56 normal ovulatory women were taken as controls. Their fasting insulin hormone, intelectin-1, anti-Mullerian hormone, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), estradiol (E2) and testosterones (T) were determined by ELISA methods. BMI, glucose and quantitative insulin sensitivity check index as well as IR was determined by the homeostasis model assessment.RESULTS: A significant changes (P<0.05) were seen in the level of homeostasis model assessment-IR, E2 and T. Levels of anti-Mullerian hormone, LH, LH/FSH ratio and prolactin were significantly (P<0.01) increased and level of intelectin-1 and E2/T ratio were significantly (P<0.01) decreased, while quantitative insulin sensitivity check index level was not significantly different (P>0.05) between the patients (1°PCOS and 2°PCOS) and control groups. On the other hand, our data reported that FSH level was significantly (P<0.05) lower in obese and higher in non-obese patients with PCOS as compared to control group.CONCLUSION: Levels of intelectin-1 and endocrinological hormones have significantly associated with body mass index, IR and physical activity in patients and normal groups and the strategies that can modulate levels of these parameters would improve metabolic disarrangements in women with PCOS.

Adenoma hipofisario ectópico del seno esfenoidal persistente tras cirugía manejado con tratamiento conservador / Ectopic pituitary adenoma in the sphenoid sinus persistent after surgery managed with conservative treatment

Los adenomas hipofisarios ectópicos (EPA) constituyen un reto diagnóstico, dada su escasa prevalencia y variada presentación en la que puede incluirse un síndrome de hipersecreción de hormonas hipofisarias. La clínica suele ser larvada e inespecífica, no presentan ninguna característica radiológica diferencial y el diagnóstico habitualmente es anatomopatológico. Sin embargo, a pesar de ser tumores benignos, pueden presentar un comportamiento agresivo, con invasión ósea y difícil resección completa, por lo que un diagnóstico de sospecha precoz podría resultar en un tratamiento más eficaz y con un menor número de complicaciones. Presentamos el caso de una paciente con un adenoma hipofisario ectópico silente en el seno esfenoidal con inmunohistoquímica positiva para Hormona de crecimiento (GH) y prolactina que presentaba restos tumorales tras la intervención quirúrgica y ha sido manejada con tratamiento médico conservado, con buenos resultados.

Ectopic pituitary adenomas constitute a diagnostic challenge, given their low prevalence and varied presentation in which a pituitary hormone hypersecretion syndrome may be included. Clinical symptoms are usually latent and nonspecific, they have no differential radiological characteristics and the diagnosis is usually anatomopathological. However, despite being benign tumors, they can exhibit aggressive behavior, with bone invasion and difficult complete resection, so a diagnosis of early suspicion could result in more effective treatment and fewer complications. We present the case of a patient with a silent ectopic pituitary adenoma in the sphenoid sinus with positive immunohistochemistry for Growth Hormone (GH) and prolactin who had tumor remnants after surgery and was managed with conservative medical treatment, with good results.

Spontaneously Regressed Rathke's Cleft Cyst

We report two rare cases of spontaneously regressed Rathke's cleft cyst (RCC). A 52-year-old woman presented with headache. A pituitary hormone study was normal. Brain magnetic resonance imaging (MRI) showed a 0.45-cm³ cystic sellar lesion. The cyst was hyperintense on T1-weighed imaging and hypointense on T2-weighted imaging without rim enhancement, comparable to a RCC. Six months later, brain MRI showed no change in the cyst size. Without any medical treatments, brain MRI 1 year later revealed a spontaneous decrease in cyst volume to 0.05 cm³. A 34-year-old woman presented with headache and galactorrhea lasting 1 week. At the time of the visit, the patient's headache had disappeared. Her initial serum prolactin level was 81.1 ng/mL, and after 1 week without the cold medicine, the serum prolactin level normalized to 11.28 ng/mL. Brain MRI showed a RCC measuring 0.71 cm³. Without further treatments, brain computed tomography 6 months later showed a spontaneous decrease in cyst volume to 0.07 cm³. Another 6 months later, brain MRI revealed that the cyst had remained the same size. Neither patient experienced neurological symptoms, such as headache or visual disturbance, during the period of cyst reduction. The RCCs in both patients underwent spontaneous regression without any medical treatment during a period of 6 months to 1 year. Although spontaneous regression of a RCC is rare, it is still possible and a sufficient follow-up period should be considered.

Serum Prolactin and Bone Mineral Density in Schizophrenia: A Systematic Review

The relationship between serum prolactin and bone mineral density (BMD) in schizophrenia is unclear. We conducted a literature review of databases from inception until December 2018 for cross-sectional, case-control, prospective and retrospective studies analyzing correlations between serum prolactin and BMD measured using dual energy X-ray absorptiometry or quantitative ultrasound at any skeletal site in people with schizophrenia. Data was summarized with a best evidence synthesis. This review identified 15 studies (1 longitudinal study, 10 cross-sectional and 4 case-control studies; 1,360 individuals with a psychotic disorder; mean age 45.1 ± 9.4 [standard deviation] years, female 742 [54.6%], mean illness duration 17.7 ± 11.3 years) assessing the relationship between serum prolactin and BMD in schizophrenia. There was a statistically significant inverse correlation between serum prolactin and BMD identified in eight of the studies (53% of all studies), suggesting mixed evidence for an association between serum prolactin and BMD. Of those studies which identified a significant inverse correlation between serum prolactin and BMD (n = 5), 152 (52.1%) of patients were treated with prolactin raising antipsychotics, compared to 197 (48.1%) of patients in those studies which did not identify a significant correlation between prolactin and BMD. Available studies cannot resolve the link between excess prolactin and reduced BMD in schizophrenia. Future studies should be longitudinal in design and combine measures of serum prolactin along with other risk factors for reduced BMD such as smoking and vitamin D and sex hormone levels in assessing the relationship between prolactin and BMD in schizophrenia.

Switching Antipsychotics to Blonanserin in Patients with Schizophrenia: An Open-label, Prospective, Multicenter Study

OBJECTIVE: This study was performed to investigate the efficacy and tolerability of blonanserin in schizophrenic patients who were previously treated with other antipsychotics but, due to insufficient response, were switched to blonanserin. METHODS: A total of 52 patients with schizophrenia who were unresponsive to treatment with antipsychotic monotherapy or combination therapy were recruited into this 12-week, open-label, prospective, multicenter study. Patients were switched to blonanserin from their existing antipsychotics over a maximum 2-week tapering-off period. Efficacy was primarily evaluated using the 18-item Brief Psychiatric Rating Scale (BPRS). Assessments were performed at baseline, and at weeks 1, 2, 4, 8, and 12. RESULTS: Switching to blonanserin resulted in a significant decrease in the mean total score on the BPRS from baseline (56.8 ± 9.4) to week 12 (42.1 ± 13.8, p < 0.001). The most common adverse events were extrapyramidal symptoms (n = 12, 23.1%), insomnia (n = 10, 19.2%), and emotional arousal (n = 6, 11.5%). Overweight or obese patients (body mass index ≥ 23 kg/m2, n = 33) who switched to blonanserin exhibited significant weight loss from 75.2 ± 9.3 kg at baseline to 73.5 ± 9.2 kg at week 12 (p = 0.006). The total cholesterol (baseline, 236.1 ± 47.6 mg/dl; endpoint [week 12], 209.9 ± 28.0 mg/dl; p = 0.005) and prolactin levels (baseline, 80.0 ± 85.2 ng/ml; endpoint [week 12], 63.2 ± 88.9 ng/ml; p = 0.003) were also significantly improved in patients with hypercholesterolemia or hyperprolactinemia. CONCLUSION: The results of the present study suggest that switching to blonanserin may be an effective strategy for schizophrenic patients unresponsive to other antipsychotic treatments.