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- Effects of Parity and Serum Prolactin Levels on the Incidence and Regression of DMBA-Induced Tumors in OFA hr/hr Rats. [Journal Article]
- Biomed Res Int 2014.:210424.
Prolactin (PRL) is a key player in the development of mammary cancer. We studied the effects of parity or hyperprolactinemia on mammary carcinogenesis in OFA hr/hr treated with 7,12-dimethylbenzanthracene. They were divided into three groups: nulliparous (Null), primiparous (PL, after pregnancy and lactation), and hyperprolactinemic rats (I, implanted in the arcuate nucleus with 17β-estradiol). The tumor incidence was similar in the three groups. However, a higher percentage of regressing tumors was evident in the PL group. Serum PRL, mammary development, and mammary β-casein content were higher in I rats compared to Null. The expression of hormone receptors was similar in the different groups. However, mammary tissue from PL rats bearing tumors had increased expression of PRL and estrogen alpha receptors compared to rats free of tumors. Our results suggest that serum PRL levels do not have relevance on the incidence of tumors, probably because the low levels of PRL in OFA rats are not further decreased by PL like in other strains. However, supraphysiological levels of PRL affect carcinogenesis. PL induces regression of the tumors due to the differentiation produced on the mammary cells. Alterations in the expression of hormonal receptors may be involved in progression and regression of tumors.
- Hypothalamic pituitary dysfunction amongst nasopharyngeal cancer survivors. [JOURNAL ARTICLE]
- Pituitary 2014 Aug 19.
Radiation fields for nasopharyngeal cancer (NPC) include the base of skull, which places the hypothalamus and pituitary at risk of damage. We aimed to establish the prevalence, pattern and severity of hypothalamic pituitary (HP) dysfunction amongst NPC survivors.We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function.Hypopituitarism was present in 82 % of patients, 30 % single axis, 28 % two axes, 18 % three axes and 6 % four axes deficiencies. Somatotroph deficiency was most common (78 %) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40 % (4 complete/16 partial), 22 and 4 % of the patients respectively. Hyperprolactinaemia was present in 30 % of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01.Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.
- Ectopic Prolactin Secretion From a Perivascular Epithelioid Cell Tumor (PEComa). [JOURNAL ARTICLE]
- J Clin Endocrinol Metab 2014 Aug 15.:jc20142623.
Background: The diagnosis of ectopic pituitary hormone secretion requires abnormally high circulating hormone levels, absence of a pituitary tumor and localization of the hormone in question to the extrapituitary malignant neoplasm. No case of a malignant solid tumor producing prolactin has been documented thus far. Case report: A 47-year old woman presented with amenorrhea and galactorrhea of 3 years' duration. Serum prolactin ranged from 300 to > 900 ng/ml, and other pituitary and thyroid indices were normal, including testing for macroprolactinemia. Pituitary MRI revealed a partially empty sella but no tumor. Cabergoline 0.5 mg twice weekly did not affect her prolactinemia (1700 to 1900 ng/ml), and the medication was stopped. In the meantime, she developed abdominal pain, and a computed tomography scan showed a 17 x 13 x 8 cm mass abutting the distal stomach, proximal duodenum, and right colon. After the tumor was excised, her galactorrhea resolved, menstrual periodicity resumed within the first month, and serum prolactin fell to 5 ng/ml. Pathological examination of the excised tumor was consistent with perivascular epithelioid cell tumor (PEComa). Between 5-10% of the tumor cells were strongly positive for prolactin on immunohistochemistry. RT-PCR detected prolactin mRNA in the tumor cell extract confirming the diagnosis of ectopic prolactin synthesis and secretion. Conclusion: We present the first example of massive and symptomatic hyperprolactinemia due to ectopic prolactin production by a solid extrapituitary mesenchymal tumor confirmed with both mRNA analysis and immunohistochemistry. Ectopic prolactin secretion should be suspected in patients with a prolactin >200 ng/ml and negative sellar MRI.
- Different Effects Of Cabergoline And Bromocriptine On Metabolic And Cardiovascular Risk Factors In Patients With Elevated Prolactin Levels. [JOURNAL ARTICLE]
- Basic Clin Pharmacol Toxicol 2014 Aug 13.
Hyperprolactinaemia is suggested to be associated with metabolic and hormonal complications. No previous study has compared the effect of different dopamine agonists on plasma lipids, carbohydrate metabolism markers and cardiovascular risk factors in patients with elevated prolactin levels. The study included eight bromocriptine-resistant women with prolactinoma (group 1) and twelve matched women with hyperprolactinaemia unrelated to prolactinoma (group 2). Group 1 was then treated with cabergoline, while group 2 with bromocriptine. Plasma lipids, glucose homeostasis markers and plasma levels of prolactin, insulin-like growth factor-1 (IGF-1), and cardiovascular risk factors were assessed before and after 6 months of therapy. Both treatments normalized plasma prolactin levels. Cabergoline reduced triglycerides, 2-hr post-challenge plasma glucose, the homeostatic model assessment of insulin resistance (HOMA-IR), and circulating levels of IGF-1, free fatty acids (FFA), uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen, as well as increased HDL-cholesterol and 25-hydroxyvitamin D. With the exception of a reduction in HOMA-IR, bromocriptine treatment produced no significant effect on the investigated biomarkers. Cabergoline was superior to bromocriptine in affecting 2-hr post-challenge plasma glucose levels, HOMA-IR, as well as circulating levels of IGF-1, FFA, uric acid, hsCRP, homocysteine, fibrinogen and 25-hydroxyvitamin D. Our results may suggest that cabergoline is superior to bromocriptine when it comes to affecting atherogenic dyslipidaemia, insulin sensitivity and circulating levels of cardiovascular risk factors in hyperprolactinaemic patients. These findings seem to support previous observations that cabergoline may be a better treatment for patients with elevated prolactin levels than bromocriptine. This article is protected by copyright. All rights reserved.
- Treatment of hyperprolactinemia in post-menopausal women: pros. [JOURNAL ARTICLE]
- Endocrine 2014 Aug 12.
The incidence of hyperprolactinemia in women peaks during the 3rd-4th decade and then greatly decreases after the menopause. Apart from the effects on the hypothalamic-pituitary-gonadal axis, prolactin can act directly on bone metabolism. Hyperprolactinemia is a recognized cause of secondary osteoporosis, and treatment with dopamine agonists can lead to improved BMD. Moreover, hyperprolactinemia has been linked to weight gain and insulin resistance, which can be ameliorated following medical treatment. Although relatively rare, prolactinomas can be observed in post-menopausal women and are frequently large and invasive; dopamine agonists appear to be as effective in these patients as in younger women to induce reduction of prolactin levels and tumour shrinkage. Here, we review data potentially favouring medical treatment with dopamine agonists in post-menopausal women diagnosed with hyperprolactinemia.
- Randomized controlled trial comparing changes in serum prolactin and weight among female patients with first-episode schizophrenia over 12 months of treatment with risperidone or quetiapine. [Journal Article]
- Shanghai Arch Psychiatry 2014 Apr; 26(2):88-94.
Increased serum prolactin and weight gain are common side effects of atypical antipsychotics but few studies have assessed the long-term pattern of these adverse effects.Compare the effects of risperidone and quetiapine on serum prolactin and weight over 12 months of treatment among female patients with first-episode schizophrenia.Eighty female inpatients with first-episode schizophrenia were randomly assigned to receive risperidone (n=40) or quetiapine (n=40) for 12 months. Prolactin concentration, weight and height were measured one day before starting treatment and 1, 3, 6, 9 and 12 months after initiating treatment. Severity of symptoms was assessed at the same time periods using the Positive and Negative Syndrome Scale (PANSS).Thirty-one patients in the risperidone group and 33 patients in the quetiapine group completed the 12 months of treatment. PANSS scores decreased at each follow-up assessment for both groups; the improvement was significantly greater in the risperidone group after 3 months and 6 months of treatment but by the 9th month of treatment the level of improvement in the two groups was similar. In the quetiapine group serum prolactin remained stable throughout the 12 months but in the risperidone group the serum prolactin level increased 3.5- to 5.2-fold over the one-year follow-up. Weight gain was seen in both groups, particularly during the first 3 months of treatment: 62% of the increase in BMI in both groups had occurred by the end of the 3rd month of treatment. No between-group differences in weight changes were observed. The correlation between changes in weight and changes in prolactin levels were weakly positive: rs=0.17(p=0.104) in the risperidone group and r=0.07 (p=0.862) in the quetiapine group.Risperidone and quetiapine had similar efficacy in the first year of treatment of first-episode schizophrenia though risperidone was more rapidly effective. Use of risperidone was associated with chronic hyperprolactinemia but this did not occur with quetiapine. Long-term use of both drugs was associated with sustained weight gain; the timing and magnitude of the weight gain is similar for the two drugs. Weight gain was not strongly related to changes in prolactin levels.
- Sulpiride-induced hyperprolactinemia in mature female rats: evidence for alterations in the reproductive system, pituitary and ovarian hormones. [Journal Article]
- Int J Fertil Steril 2014 Jul; 8(2):193-206.
The prevalence of hyperprolactinemia following administration of conven- tional antipsychotic drugs requires further investigation. The current study is designed to evaluate the effect of sulpiride (SPD)-induced hyperprolactinemia on alterations to ovarian follicular growth, gonadotropins, and ovarian hormones and to analyze the extent of potential problems in mammary glands.A total of 40 albino Wistar rats were divided into four groups: control (no treatment), control-sham (0.3 ml olive oil), low dose SPD (20 mg/kg) and high dose SPD (40 mg/kg). All compounds were intraperitoneally (IP) administered for a period of 28 days.After 28 days, we dissected the rats' ovarian tissues, uterine horns and mammary glands which were sent for histological analyses. We counted the numbers of normal, atretic follicles and corpora lutea (CL). Serum levels of prolactin (PRL), estradiol, progesterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were evaluated. SPD-administered animals showed sporadic follicular atresia in different sizes associated with higher numbers of CL on the ovaries. The mammary glands exhibited features of galactorrhea. There was remarkable (p<0.05) elevation in SPD-administered animals' uterine horn endometrium, myometrium and perimetrium thicknesses. The serum levels of PRL and progesterone significantly (p<0.05) increased, while the serum concentration of estradiol, LH and FSH notably (p<0.05) decreased according to the SPD administered dose. No histological and biological changes occurred in control-sham animals. SPD-induced animals had unsuccessful attempts at mating and decreased pregnancy rates.The present findings suggest that SPD-induced disturbances depend on PRL level. In addition, an increased PRL level is largely dependent on the administered doses of SPD.
- Hormonal causes of recurrent pregnancy loss (RPL). [REVIEW]
- Hormones (Athens) 2014 Jul; 13(3):314-322.
Endocrine disorders play a major role in approximately 8% to 12% of recurrent pregnancy loss (RPL). Indeed, the local hormonal milieu is crucial in both embryo attachment and early pregnancy. Endocrine abnormalities, including thyroid disorders, luteal phase defects, polycystic ovary syndrome, hyperprolactinaemia and diabetes have to be evaluated in any case of RPL. Moreover, elevated androgen levels and some endocrinological aspects of endometriosis are also factors contributing to RPL. In the present article, we review the significance of endocrine disease on RPL.
- McCune-Albright Syndrome: A Detailed Pathological And Genetic Analysis of Disease Effects in an Adult Patient. [JOURNAL ARTICLE]
- J Clin Endocrinol Metab 2014 Jul 25.:jc20141291.
Context: McCune Albright syndrome (MAS) is a clinical association of endocrine and non-endocrine anomalies caused by post-zygotic mutation of the GNAS1 gene, leading to somatic activation of the stimulatory α subunit of G protein (Gsα). Important advances have been made recently in describing pathological characteristics of many MAS-affected tissues, particularly pituitary, testicular and adrenal disease. Other rarer disease related features are emerging. Objective: To study pathological and genetic findings of MAS on a tissue-by-tissue basis in classically and non classically affected tissues. Design: A comprehensive autopsy and genetic analysis Setting: Tertiary referral University Hospital Patients: Adult male patient with MAS and severe disease burden including gigantism Intervention(s): Clinical, hormonal and radiographic studies; gross and microscopic pathology analyses, conventional PCR and droplet digital PCR analyses of affected and non affected tissues Main Outcome Measure: Pathological findings, presence of GNAS1 mutations Results: The patient was diagnosed with MAS syndrome at six years of age based on the association of café-au-lait spots and radiological signs of polyostotic fibrous dysplasia. Gigantism developed and hyperprolactinemia, hypogonadotropic hypogonadism and hyperparathyroidism were diagnosed throughout adult period. The patient died at the age of 39 from pulmonary embolism. A detailed study revealed mosaiscism for the p.R201C GNAS mutation distributed across many endocrine and non-endocrine tissues. These genetically implicated tissues included rare or previously undescribed disease associations including primary hyperparathyroidism, and hyperplasia of the thymus and endocrine pancreas. Conclusions: This comprehensive pathological study of a single patient highlights the complex clinical profile of MAS and illustrates important advances in understanding the characteristics of somatic GNAS1 related pathology across a wide range of affected organs.
- Diagnosis of prolactinoma in two male-to-female transsexual subjects following high-dose cross-sex hormone therapy. [JOURNAL ARTICLE]
- Andrologia 2014 Jul 25.
Male-to-female transsexual persons use oestrogens + antiandrogens to adapt their physical bodies to the female sex. Doses are usually somewhat higher than those used by hypogonadal women receiving oestrogen replacement. Particularly in cases of self-adminstration of cross-sex hormones, doses may be very high. Oestrogens are powerful stimulators of synthesis and release of prolactin and serum prolactin levels are usually somewhat increased following oestrogen treatment. Prolactinomas have been reported in male-to-female transsexual persons, both after use of high and conventional doses of oestrogens but remain rare events. We report two new cases of prolactinomas in male-to-female transsexual persons, one in a 41-year-old subject who had used nonsupervised high-dose oestrogen treatment since the age of 23 years and another one in a 42 year old who had initiated oestrogen treatment at the age of 17 years. Their serum prolactin levels were strongly increased, and the diagnosis of a pituitary tumour was confirmed by imaging techniques. Both cases responded well to treatment with cabergoline treatment whereupon serum prolactin normalised. Our two cases are added to the three cases of prolactinomas in the literature in persons who had used supraphysiological doses of oestrogens.