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- Color Doppler analysis of uterine, spiral, and intraovarian artery blood flow before and after treatment with cabergoline in hyperprolactinemic patients. [JOURNAL ARTICLE]
- Gynecol Endocrinol 2014 Sep 15.:1-4.
Abstract Prolactin (PRL) may have stimulatory effects on vascular resistance. We aimed to analyze uterine, spiral, and intraovarian artery blood flow by Doppler ultrasonography in hyperprolactinemic patients prior to and after treatment with cabergoline. The study was conducted in Sisli Etfal Training and Research Hospital gynecology outpatient clinic between 1 March 2010 and 30 September 2011. Twenty-four women with symptomatic hyperprolactinemia in reproduction age were included in the study. All hyperprolactinemic patients were studied prior to and following the suppression of circulating PRL levels by cabergoline. Patients were examined by standard B-mod and color transvaginal ultrasonography. Pulsality index (PI), resistance index (RI), and systolic/diastolic ratio (S/D) were recorded. The median PRL value was 86 (62-120) ng/ml before treatment and 4.0 (2.5-6.4) ng/ml after the treatment (p < 0.001). We found a significant association among PRL, uterine, spiral, and intraovarian artery RI with linear regression analysis (p < 0.001 for all three arteries). Uterine, spiral, and intraovarian artery PI (p = 0.021, p < 0.001, and p < 0.001, respectively) and RI (p = 0.001, p < 0.001, and p < 0.001, respectively) significantly decreased after cabergoline treatment. In conclusion, this is a pilot study which shows for the first time that PRL increases the uterine, endometrial, and intraovarian vascular resistance and cabergoline reverses this effect.
- Serotonergic 5-HT2A/2C receptors are involved in prolactin secretion in hyperestrogenic rats. [JOURNAL ARTICLE]
- Neurosci Lett 2014 Sep 8.
Serotonin (5-HT) has been shown to participate in prolactin secretion through a complex process resulting in both positive and negative effects. Estrogen has also been recognized as being involved in this serotonergic effect on prolactin release. Therefore, the aim of the present study was to assess whether estradiol modulates serotonergic involvement in prolactin secretion though 5-HT1A and/or 5-HT2A/2C receptors. Ovariectomized female Wistar rats, treated for 2 weeks with estrogen to induce a hyperprolactinemic status (hyperestrogenic rats) or with sunflower oil vehicle (hypoestrogenic rats), were injected daily with normal saline solution or 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), an 5-HT2A/2C receptor agonist, for 4 days. Other groups of ovariectomized animals received 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) or pindolol, an agonist and antagonist of the 5-HT1A receptor respectively, on the last day of treatment with estrogen or vehicle. Prolactin levels were compared among groups in each experiment under the distinct drug treatments. MK-212 was found to increase prolactin concentrations both in hyper- and hypoestrogenic females compared to controls (p<0.05). In contrast, prolactin levels remained similar to those of controls both in hyperestrogenic animals treated with 8-OH-DPAT and pindolol and in hypoestrogenic rats administered the same treatments. In conclusion, our findings indicate the involvement of 5-HT2A/2C receptors on prolactin release through serotonergic pathways in female animals, especially in hyperestrogenic states.
- Antimullerian hormone in cases of different reproductive pathologies. [Journal Article]
- Georgian Med News 2014 Jul-Aug; (232-233):16-21.
The aim of this study was to define the importance of determination of AMH during different reproductive pathologies and to identify the correlations between the tests currently used in ovarian reserve assessment (AMH, FSH, AFC) in different age groups of infertile woman. Study population consisted of 153 women. In 41 women with different reproductive pathologies we evaluate the values of AMH. 112 women with infertility were divided into the three age groups: group I <35 years (n=39); group II 35-40 years (n=31); and group III >40 years (n=42). AMH, FSH and AFC were determined on days 2-3 of menstrual cycle. We evaluated the AMH values during different reproductive pathologies (n=41) and found that: in cases of gonadal dysgenesis and ootesticular disorders AMH levels are decreased. In cases of POI AMH levels were extremilly low. Normal levels of AMH were detected in cases of Hyperprolactinemia and Hypogonadotropic hypogonadism. In patients with PCOS AMH levels were increased. The correlation analysis between ovarian reserve tests was performed in 112 infertile women. Generally, age is in a significant high negative correlation with AMH level (rs=-0.67, p<0.0001) and AFC (rs=-0.55, p<0.0001), and in positive correlation with FSH (rs=0.38, p<0.0001). AMH negatively correlates with FSH (rs=-0.48, p<0.0001) and positively with AFC (r=0.71, p=0.0001). There is a moderate negative relation between FSH and AFC (r=-0.41, p=0.0001) and moderate positive relation between age and FSH (rs=0.38, p<0.0001). The correlation analysis performed in separate groups showed that AMH and AFC in all three study groups correlates positively and are statistically significant (r=0.57, p<0.0001; r=0.69, p<0.0001; r=0.47, p<0.002 respectively). Whereas statistically significant correlation between FSH and AMH detected only in the first and second age groups (r=-0.41, p<0.02; r=-0.55, p<0.0001 respectively). Statistically significant correlation between FSH and AFC revealed only in the third age group (r=-0.42, p<0.006), as well as between age and AFC only in first age group (r=-0.35, p<0.03). Nowadays, among used ovarian reserve assesment tests AMH should be considered to be more reliable, than FSH. Serum AMH level is in strongly positive correlation with AFC. Using of AMH measurement in combination with AFC may improve the evaluation of ovarian reserve. Determination of AMH also may be of diagnostic value in cases of different reproductive pathologies.
- Persistence of intrasellar trigeminal artery and simultaneous pituitary adenoma: description of two cases and their importance for the differential diagnosis of sellar lesions. [Journal Article]
- Arq Bras Endocrinol Metabol 2014 Aug; 58(6):661-5.
Persistent trigeminal artery (PTA) is the most frequent embryonic communication between the carotid and vertebrobasilar systems. However, hormonal changes or the association of PTA with other sellar lesions, such as pituitary adenomas, are extremely rare. The aim of the present study was to report two patients with intrasellar PTA and simultaneous pituitary adenoma in order to emphasize the importance of differential diagnoses for sellar lesions. Case 1. A female patient, 41 years old, was admitted with a history of chronic headache (> 20 years). Pituitary magnetic resonance imaging (MRI) showed a rounded lesion in the left portion of the pituitary gland suggestive of adenoma (most likely clinically non-functioning adenoma). In addition to this lesion, the MRI demonstrated ecstasy of the right internal carotid artery and imaging suggestive of an intrasellar artery that was subsequently confirmed by an angio-MRI of the cerebral vessels as PTA. Case 2. A female patient, 42 years old, was admitted with a history of amenorrhea and galactorrhea in 1994. Laboratorial investigation revealed hyperprolactinemia. Pituitary MRI showed a small hyposignal area in the anterior portion of pituitary gland suggestive of a microadenoma initiated by a dopaminergic agonist. Upon follow-up, aside from the first lesion, the MRI showed a well delineated rounded lesion inside the pituitary gland, similar to a vessel. Angio-MRI confirmed a left primitive PTA. Failure to recognize these anomalous vessels within the sella might lead to serious complications during transsphenoidal surgery. Therefore, although their occurrence is uncommon, a working knowledge of vascular lesions in the sella turcica or pituitary gland is important for the differential diagnosis of pituitary lesions, especially pituitary adenomas.
- The pituitary gland in patients with Langerhans cell histiocytosis: a clinical and radiological evaluation. [JOURNAL ARTICLE]
- Endocrine 2014 Sep 11.
Langerhans cell histiocytosis (LCH) is a rare disease in which the most common endocrine manifestation is diabetes insipidus (DI). Data on anterior pituitary function in patients with LCH are limited. Thus, the present study investigated anterior pituitary function in LCH patients with DI via the evaluation of clinical and radiological findings at disease onset and during follow-up. The present study retrospectively evaluated nine patients with LCH (five males and four females). All diagnoses of LCH were made following histological and/or immunophenotypic analyses of tissue biopsies, bronchoalveolar lavage, or cerebrospinal fluid (CSF). Basal and, if necessary, dynamic pituitary function tests were used to assess anterior pituitary function, and magnetic resonance imaging (MRI) scans were used to image the pituitary. The LCH treatment modality was based on organ involvement. The mean age at onset of DI was 27.6 years (range 15-60 years). One patient (11 %) exhibited single organ involvement, while eight patients (89 %) displayed multisystem organ involvement. On admittance, one patient had hypogonadotropic hypogonadism, one patient exhibited panhypopituitarism [hypogonadotropic hypogonadism, central hypothyroidism, hypocortisolism, and growth hormone (GH) deficiency], and four patients (44 %) displayed hyperprolactinemia. The MRI data revealed infundibular enlargement in seven patients (78 %), a thalamic mass in one patient (11 %), and the absence of the bright spot in all patients. A single patient (11 %) showed a mass in the pons that had a partially empty sella. The patients were treated with radiation therapy (RT), chemotherapy (CT), or a combination of both (RT + CT) and were followed up for a median of 91.8 months (range 2-318 months). Seven patients were assessed during the follow-up period, of whom four patients (57.1 %) developed anterior pituitary hormone deficiency, three (43 %) were diagnosed with GH deficiency, and one (14 %) exhibited gonadotropin deficiency. The gonadotropin deficiency in the patient, which was diagnosed on admittance, was resolved during the follow-up period. DI persisted in all patients, and the conditions of the seven patients who have remained on follow-up are stable. In the present study, patients with LCH exhibited altered function in the anterior pituitary as well as the posterior pituitary, which may be due to the natural course of the disease or the effects of treatment. The present findings indicate that anterior pituitary function should be assessed in LCH patients on admittance and during follow-up, especially in LCH patients with multisystem organ involvement.
- Prolactin regulation of kisspeptin neurons in the mouse brain and its role in the lactation-induced suppression of kisspeptin expression. [JOURNAL ARTICLE]
- J Neuroendocrinol 2014 Sep 10.
Hyperprolactinaemia is a major cause of infertility in both males and females, but the mechanism by which prolactin inhibits the reproductive axis is not clear. The aim of the present study was to test the hypothesis that elevated prolactin causes suppression of kisspeptin expression in the hypothalamus, resulting in reduced release of GnRH and consequent infertility. In estrogen-treated OVX mice, chronic prolactin-treatment prevented the rise in LH seen in vehicle-treated mice. Kiss1 mRNA was significantly suppressed in both the rostral periventricular region of the third ventricle (RP3V) and arcuate nucleus following prolactin treatment. Exogenous prolactin treatment induced pSTAT5 in kisspeptin neurons, and suppression of endogenous prolactin using bromocriptine reduced levels of pSTAT5 in kisspeptin neurons, suggesting that prolactin acts directly on kisspeptin neurons. In contrast, fewer than 1% of GnRH neurons expressed pSTAT5 in either diestrous or lactating mice. As reported previously, there was significant suppression of kisspeptin mRNA and protein in the RP3V on day 7 of lactation, but not in the arcuate nucleus. Bromocriptine treatment significantly increased Kiss1 mRNA expression in the RP3V, although not to diestrous levels. Unilateral thelectomy, to eliminate sensory inputs from nipples on one side of the body, failed to alter the reduction in the number of kisspeptin neurons observed in the RP3V. These data demonstrate that chronic prolactin administration suppressed serum LH, and reduced Kiss1 mRNA levels in both the RP3V and ARN, consistent with the hypothesis that prolactin-induced suppression of kisspeptin secretion might mediate the inhibitory effects of prolactin on GnRH secretion. During lactation, however, the suppression of Kiss1 mRNA in the RP3V was only partially reversed by the administration of bromocriptine to block elevated levels of prolactin, suggesting that while elevated prolactin contributes to lactational anovulation, additional non-neural factors must also contribute to the lactation-induced suppression of kisspeptin neurons. This article is protected by copyright. All rights reserved.
- Aborted sudden cardiac death and a mother with suspected metabolic myopathy. [Journal Article]
- Clin Med Insights Cardiol 2014.:67-9.
Aborted sudden cardiac death (SCD) has not been reported as initial manifestation of cardiac involvement in metabolic myopathy (MM). A 20-year-old female with a previous history of three syncopes, hyperhidrosis, and recurrent tick bites experienced aborted SCD. Her mother presented with MM, and a history of pituitary adenoma, nephroptosis, arterial hypertension, depression, migraine, goiter, pancreatitis, osteoporosis, hyperhidrosis, multiple muscle ruptures, and hyperlipidemia. After a few days of disorientation and amnesia, the young female recovered completely. Clinical neurological examination was noticeable for partial ophthalmoparesis and mild hyperprolactinemia. She received an implantable cardioverter defibrillator, which did not discharge so far. Recurrent syncopes and aborted SCD may be the initial manifestation of MM with multiple organ involvement. The family history is important in cases with aborted SCD to guide the diagnostic work-up. Phenotypic heterogeneity between the family members may be an indicator of MM.
- The effects of additional treatment with terguride, a partial dopamine agonist, on hyperprolactinemia induced by antipsychotics in schizophrenia patients: a preliminary study. [Journal Article]
- Neuropsychiatr Dis Treat 2014.:1571-6.
Hyperprolactinemia is a frequent consequence of treatment with antipsychotics. Earlier studies have indicated that terguride, which is a partial dopamine agonist, reduces the prolactin levels that are induced by prolactinemia. Thus, we examined the dose effects of adjunctive treatment with terguride on the plasma concentrations of prolactin in patients with elevated prolactin levels resulting from antipsychotic treatment. Terguride was concomitantly administered to 20 schizophrenic patients (10 males and 10 females) receiving paliperidone and risperidone. The dose of terguride was 1.0 mg/day. Sample collections for prolactin were conducted before terguride (baseline) and 2-4 weeks after administration. The samples were obtained after the morning dose of terguride. The average (± standard deviation) plasma prolactin concentration during terguride coadministration was significantly lower than the baseline concentration in females (82.3±37.1 ng/mL versus 56.5±28.5 ng/mL, P<0.01) but not in males (28.8±18.0 ng/mL versus 26.2±13.1 ng/mL, not significant). Additionally, a significant correlation between the ratio of prolactin reduction and the baseline prolactin concentration was identified in males (r s=-0.638, P<0.05) but not in females (r s=-0.152, not significant). Many patients complained of various adverse events following terguride administration, such as insomnia, agitation, and/or the aggravation of hallucinations. This study suggests that additional treatment with terguride decreases the prolactin concentrations in females experiencing high prolactin levels as a result of antipsychotic treatment. However, its utility for schizophrenia may be diminished because of its low tolerability.
- Effects of hyperprolactinemia and ovariectomy on the tibial epiphyseal growth plate and bone formation in mice. [Journal Article]
- Rev Bras Ginecol Obstet 2014 Aug; 36(8):359-66.
To evaluate the effects of ovariectomy and the hyperprolactinemia procedure in the tibial epiphyseal growth plate of female mice.In this study, the epiphyseal growth plate of ovariectomized (OVX) and/or rendered hyperprolactinemic female mice by 50 days of treatment with 200 μg metoclopramide (M) was evaluated morphologically, morphometrically and immuno-histochemically. Forty female and adult mice were divided into four groups according to treatment: V group - animals treated with saline solution; H group - hyperprolactinemic animals; Ovx/V group - ovariectomized animals and treated with saline solution; Ovx/H group - hyperprolactinemic and ovariectomized animals. After the treatment period, the animals were sacrificed, tibia was removed and fixed in 10% buffered formalin and decalcified in 10% formic acid. The material was immersed in paraffin and subjected to histological processing in paraffin. The sections were stained with Masson's trichrome and immunohistochemistry was carried out for the pro-apoptotic protein BCL-2. The images for the morphological and morphometric study were analyzed with the imaging program AxioVision 4.8 (Carl-Zeiss(r), Germany).The combination of hyperprolactinemia and the ovariectomy procedure decreased the number of resting chondrocytes 1.5-fold, the number of proliferative chondrocytes 1.8-fold; the percentage of resting cartilage 2.4-fold and the percentage of trabecular bone 2.1-fold, compared with respective control animals.The procedure of ovariectomy combined with the metoclopramide-induced hyperprolactinemia in female mice has showed marked bone degeneration due to significant decrease of cell proliferation in the epiphyseal growth plate and bone formation.
- Whole Exome Sequencing of Extreme Morbid Obesity Patients: Translational Implications for Obesity and Related Disorders. [JOURNAL ARTICLE]
- Genes (Basel) 2014; 5(3):709-725.
Whole-exome sequencing (WES) is a new tool that allows the rapid, inexpensive and accurate exploration of Mendelian and complex diseases, such as obesity. To identify sequence variants associated with obesity, we performed WES of family trios of one male teenager and one female child with severe early-onset obesity. Additionally, the teenager patient had hypopituitarism and hyperprolactinaemia. A comprehensive bioinformatics analysis found de novo and compound heterozygote sequence variants with a damaging effect on genes previously associated with obesity in mice (LRP2) and humans (UCP2), among other intriguing mutations affecting ciliary function (DNAAF1). A gene ontology and pathway analysis of genes harbouring mutations resulted in the significant identification of overrepresented pathways related to ATP/ITP (adenosine/inosine triphosphate) metabolism and, in general, to the regulation of lipid metabolism. We discuss the clinical and physiological consequences of these mutations and the importance of these findings for either the clinical assessment or eventual treatment of morbid obesity.