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- 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.
- [Lactation after breast plastic surgery: Literature review.] [JOURNAL ARTICLE]
- Ann Chir Plast Esthet 2014 Aug 18.
The occurrence of lactation is a rare complication of breast plastic surgery. During the course of his practice, the plastic surgeon will probably encounter this complication. The goal of this article is to carry out a literature review of all published galactorrhea and/or galactocele cases following a breast-reduction or a breast-augmentation, representing a total of 34 cases reported in 21 articles. The physiopathology of this complication is linked to an inappropriate secretion of prolactin in a surgical context. The factors favoring this complication would be the number of pregnancies, a history of recent and extensive nursing, and the intake of certain medicines such as an oestro-progestative pill. The main symptom of this complication is the occurrence of a uni- or bilateral galactorrhea, on average 12.6 days after the surgery. The main differential diagnosis is a postoperative infection. The explorations presented a hyperprolactinemia in 69% of cases. No biological inflammatory syndrome was reported. A fluid collection evoking a galactocele was visible on the ultrasound in 65% of cases. One case of prolactin-secreting pituitary adenoma was reported. Depending on the case, the treatment varied from a simple surveillance to the association of a dopamine agonist, an antibiotic therapy, and a surgical revision. A diagnostic and therapeutic management strategy is proposed.
- Surgical treatment of prolactinomas--our experience. [Journal Article]
- Coll Antropol 2014 Jun; 38(2):571-6.
The dilemma of whether to apply surgical or drug treatment to prolactinomas has been ongoing for the past 30 years. The aim of this study is to compare the early postoperative values of prolactin (PRL) in two groups of patients with prolactinomas: those who underwent primary surgical-treatment, and those who underwent surgery after a dopamine agonist (DA) therapy. We present the results of surgical treatment on a series of 161 patients with prolactinomas. Surgery was the primary treatment in 65 patients, while 96 patients had surgery following a long-term treatment with a DA. All surgically treated prolactinomas were operated in the standard transsphenoidal, microsurgical approach. The criteria for hyperprolactinemia remission was a PRL level under 25 ng/ml. Early normalization of PRL was achieved in 92% of those patients who underwent primary surgical-treatment, yet it was achieved in only 42% of patients who were operated on after receiving a long-term drug treatment with a DA. The highest prevalence of postoperative normalization of PRL was achieved in a group of patients with microadenomas who were primarily operated on (98%). The worst results in postoperative normalization of PRL were found in the group of patients with macroadenomas who received a long-term drug treatment with a DA first. These results show our surgical experience in treating prolactinomas. Using surgical treatment, the best clinical outcome was achieved with microprolactinomas and intrasellar, well-confined macroprolactinomas. Nevertheless, we stress the need of an individualized approach and recommend treatment in multidisciplinary centres for pituitary diseases.
- Diagnostic pitfalls of hyperprolactinemia: the importance of sequential pituitary imaging. [JOURNAL ARTICLE]
- BMC Res Notes 2014 Aug 20; 7(1):555.
The purpose of this study is to confirm whether the serum prolactin cut-off value is definitive to distinguish prolactinoma and non-functioning pituitary adenoma with hyperprolactinemia. We retrospectively reviewed patients with non-functioning pituitary adenoma, including gonadotroph cell adenoma, null cell adenoma and prolactinoma who were surgically treated at Kohnan hospital between June 2005 and March 2012. The patients without endocrinological/neurological symptom and with the tumor larger than 40 mm in diameter were excluded. According to previously reported cut-off value of serum prolactin, mild hyperprolactinemia, which is considered non-definitive (border zone) concentration between prolactinoma and non-functioning pituitary adenoma, were defined as 90 - 200 ng/ml. Ninety-five prolactinoma patients and 212 patients with non-functioning pituitary adenoma were analyzed. The serum prolactin concentration, tumor size, and clinical characteristics were statistically compared.Receiver operating characteristic (ROC) curve analysis was performed, indicating that cut-off value of serum prolactin concentration to distinguish between non-functioning pituitary adenoma and prolactinoma was 38.6 ng/ml. Although it was statistically good accuracy (the area under the curve; 0.96, sensitivity; 0.99 and specificity; 0.81), the result did not fit the clinical situation as many false-positive cases (40 of 212, 18.9%) were included. Among them, mild hyperprolactinemia were shown in 9 (4.2%) and 53 (55.8%) patients with prolactinoma and non-functioning pituitary adenoma, respectively. Four of 9 border zone patients with non-functioning pituitary adenoma were initially treated with dopamine agonists. Sequential head magnetic resonance imaging revealed no tumor shrinkage in all of them despite serum prolactin concentration was decreased. Surgery was chosen for them 24.6 months in average after the introduction of medication.Non-negligible number of patients with non-functioning pituitary adenoma presented unexpectedly high concentration of prolactin, fraught with a potential risk of misdiagnosis. While this equivocal population is not the majority, the prolactin cut-off value is not safely applicable. Especially for the patients with border zone prolactin concentration, meticulous follow up with sequential pituitary imaging is important.
- 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.