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- Hyperprolactinemia. [REVIEW]
- J Hum Reprod Sci 2013 7; 6(3):168-175.
Prolactin (PRL) is an anterior pituitary hormone which has its principle physiological action in initiation and maintenance of lactation. In human reproduction, pathological hyperprolactinemia most commonly presents as an ovulatory disorder and is often associated with secondary amenorrhea or oligomenorrhea. Galactorrhea, a typical symptom of hyperprolactinemia, occurs in less than half the cases. Out of the causes of hyperprolactinemia, pituitary tumors may be responsible for almost 50% of cases and need to be investigated especially in the absence of history of drug induced hyperprolactinemia. In women with hyperprolactinemic amenorrhea one important consequence of estrogen deficiency is osteoporosis, which deserves specific therapeutic consideration. Problem in diagnosing and treating hyperprolactinemia is the occurrence of the 'big big molecule of prolactin' that is biologically inactive (called macroprolactinemia), but detected by the same radioimmunoassay as the biologically active prolactin. This may explain many cases of very high prolactin levels sometimes found in normally ovulating women and do not require any treatment. Dopamine agonist is the mainstay of treatment. However, presence of a pituitary macroadenoma may require surgical or radiological management.
- Preclinical Atherosclerosis in Patients with Prolactinoma. [JOURNAL ARTICLE]
- Endocr Pract 2013 Dec 10.:1-15.
Objective: The aim of this study was to evaluate the effect of hyperprolactinemia on body fat, insulin sensitivity, inflammatory markers, and cardiovascular risk in patients with prolactinoma.Methods: The study included 35 untreated hyperprolactinemic patients with pituitary adenomas, and 36 age-, gender-, and BMI-matched healthy controls without any known disease. Serum glucose, insulin, homeostasis model assessment of insulin resistance, lipid profile, high sensitive C-reactive protein, and heart-type fatty acid binding protein levels were measured. Waist and hip circumference were measured in all the participants. The body fat percentage was measured, and the visceral fat and abdominal fat percentage was measured via bioelectrical impedance. In addition, carotid intima media thickness was measured using high-resolution B-mode ultrasound.Results: The serum glucose level, homeostasis model assessment of insulin resistance, triglyceride level, and waist circumference were significantly higher in the patient group than in the control group. The high sensitive C-reactive protein level and carotid intima media thickness were significantly higher in the hyperprolactinemic patients. Visceral and truncal fat percentages were significantly higher in the patients with prolactinoma. Heart-type fatty acid binding protein levels were similar in the patient and control groups, and there was a positive correlation between the prolactin and heart-type fatty acid binding protein levels.Conclusions: Based on the present findings, hyperprolactinemia is associated with preclinical atherosclerosis and metabolic abnormalities. Patients with hyperprolactinemia might experience cardiovascular disease in the long-term. Metabolic control should be achieved in addition to the control of hyperprolactinemia, in the clinical management of patients diagnosed with prolactinoma.
- Serum Prolactin and Macroprolactin Levels among Outpatients with Major Depressive Disorder Following the Administration of Selective Serotonin-Reuptake Inhibitors: A Cross-Sectional Pilot Study. [Journal Article]
- PLoS One 2013; 8(12):e82749.
Clinical trials evaluating the rate of short-term selective serotonin-reuptake inhibitor (SSRI)-induced hyperprolactinemia have produced conflicting results. Thus, the aim of this study was to clarify whether SSRI therapy can induce hyperprolactinemia and macroprolactinemia. Fifty-five patients with major depressive disorder (MDD) were enrolled in this study. Serum prolactin and macroprolactin levels were measured at a single time point (i.e., in a cross-sectional design). All patients had received SSRI monotherapy (escitalopram, paroxetine, or sertraline) for a mean of 14.75 months. Their mean prolactin level was 15.26 ng/ml. The prevalence of patients with hyperprolactinemia was 10.9% for 6/55, while that of patients with macroprolactinemia was 3.6% for 2/55. The mean prolactin levels were 51.36 and 10.84 ng/ml among those with hyperprolactinemia and a normal prolactin level, respectively. The prolactin level and prevalence of hyperprolactinemia did not differ significantly within each SSRI group. Correlation analysis revealed that there was no correlation between the dosage of each SSRI and prolactin level. These findings suggest that SSRI therapy can induce hyperprolactinemia in patients with MDD. Clinicians should measure and monitor serum prolactin levels, even when both SSRIs and antipsychotics are administered.
- A new logical insight and putative mechanism behind fluoxetine-induced amenorrhea, hyperprolactinemia and galactorrhea in a case series. [Journal Article, Review]
- Ther Adv Psychopharmacol 2013 Dec; 3(6):322-34.
With the exception of fluoxetine, all selective serotonin reuptake inhibitors (SSRIs) commonly cause hyperprolactinemia through presynaptic mechanisms indirectly via 5-hydroxytryptamine (5-HT)-mediated inhibition of tuberoinfundibular dopaminergic neurons. However, there is little insight regarding the mechanisms by which fluoxetine causes hyperprolactinemia via the postsynaptic pathway. In this text, analysis of five spontaneously reported clinical cases of hyperprolactinemia resulting in overt symptoms of amenorrhea with or without galactorrhea, were scrupulously analyzed after meticulously correlating relevant literature and an attempt was made to explore the putative postsynaptic pathway of fluoxetine inducing hyperprolactinemia. Hypothetically, serotonin regulates prolactin release either by increasing oxytocin (OT) level via direct stimulation of vasoactitive intestinal protein (VIP) or indirectly through stimulation of GABAergic neurons. The pharmacodynamic exception and pharmacokinetic aspect of fluoxetine are highlighted to address the regulation of prolactin release via serotonergic pathway, either directly through stimulation of prolactin releasing factors (PRFs) VIP and OT via 5-HT2A receptors predominantly on PVN (neurosecretory magnocellular cell) or through induction of 5-HT1A-mediated direct and indirect GABAergic actions. Prospective molecular and pharmacogenetic studies are warranted to visualize how fluoxetine regulate neuroendocrine system and cause adverse consequences, which in turn may explore new ways of approach of drug development by targeting the respective metabolic pathways to mitigate these adverse impacts.
- Management of prolactinomas during pregnancy. [Journal Article]
- Minerva Endocrinol 2013 Dec; 38(4):351-63.
Prolactinomas constitute approximately 40% of hormone-secreting pituitary tumors. In women the main clinical features are menstrual disorders and infertility. Successful treatment with dopamine agonists restores the normal function of the pituitary-gonadal axis, ovulation, and fertility. Adequate management of pregnant prolactinoma patients from the moment of conception is of particular importance for both the mother and the developing fetus. This review article presents current opinions on the course and management of pregnancies in patients with prolactin-secreting pituitary tumors. The introduction contains background information on clinical aspects of the condition, including prolactinoma treatment in women of reproductive age. Physiological changes in the pituitary during normal pregnancy are also described. The next part presents current knowledge on the effect of pregnancy on prolactinoma size, including especially the high risk of prolactinoma growth in patients with pituitary macroadenomas. Safety issues concerning the use of dopamine receptor agonists during pregnancy are also discussed, especially in terms of the risk of congenital defects in the fetus. Moreover, the article presents principles of prolactinoma management in pregnant patients, rare indications for surgical treatment during pregnancy, and the issues concerning pituitary tumor apoplexy in pregnant women, the last being a life-threatening condition. The final part of the article discusses the possible effects of pregnancy on hyperprolactinemia remission as well as on the issue of breastfeeding by mothers with prolactinoma.
- Prevalence, presentation and management of polycystic ovary syndrome in Enugu, south east Nigeria. [Journal Article]
- Niger J Med 2013 Oct-Dec; 22(4):313-6.
Polycystic ovary syndrome is the most common gynaecological endocrine disorder in women of reproductive age yet, its prevalence and management has not been documented in our area.To determine the prevalence, presentation and management of polycystic ovary syndrome among women in Enugu, south east Nigerian.A prospective descriptive study of women with polycystic ovaries seen in two major Infertility Clinics in Enugu, South East Nigeria over a 2 year period.A total of 342 women presented with infertility in the centres within the two year period, out of whom 62 had PCOS. PCOS occurred in 18.1% of women in the infertility clinics of the two institutions. The common modes of presentation were: inability to conceive (infertility) in 52 (83.9%), oligomenorrhoea in 45 (72.6%), obesity in 32 (51.6%), LH/FSH ratio > 2 in 28 (45.2%), hyperprolactinaemia in 26 (41.9%) and hirsuitism in 19 (30.6%) women. Ovulation induction was carried out in 42 of the 50 women with anovulatory infertility only. For those 42 women, the mean number of induced cycles was 2.6 = 1.7 (range: 1-6) with 33 (78.6%) of the women being able to do only 3 induced cycles or less. The ovulation induction agents used were clomiphene citrate and human menopausal gonadotrophin either singly or in combination with tamoxifen or bromocryptine. Adjunctive treatments offered consisted of weight reduction in 20 (40.0%) women, metformin in 11 (22.0%) women and dexamethasone in 10 (20.0%) women.PCOS is fairly common occurring in approximately one in six infertile Nigerian women. Infertility, oligomenorrhoea, obesity, LH/FSH ratio > 2, hyperprolactinaemia and hirsutism are the commonest presenting features. On individualized management, about two-fifths of them conceive either spontaneously or following ovulation induction, despite poor compliance to recommended drug regimen.
- Autoimmune thyroiditis: Centennial jubilee of a social disease and its comorbidity. [JOURNAL ARTICLE]
- Pathophysiology 2013 Nov 22.
The history of autoimmune thyroiditis (AIT) and its role in pathophysiology of transition from adolescent hypothalamic syndrome (obesity with rose striae) into early metabolic syndrome is reviewed. Marfanoid phenotype and chronic disequilibrium between local, autacoid-mediated and systemic, hormone-mediated regulation, typical for inherited connective tissue disorders, may promote this transition. Pathogenetic roles of hyperprolactinemia and cytokine misbalance are evaluated and discussed in its pathogenesis.
- Frequency of Hyperprolactinemia and Its Associations With Demographic and Clinical Characteristics and Antipsychotic Medications in Psychiatric Inpatients in China. [JOURNAL ARTICLE]
- Perspect Psychiatr Care 2013 Nov 20.
No study has investigated hyperprolactinemia and its risk factors in Chinese psychiatric patients. This study examined the prevalence of hyperprolactinemia and its relationship with demographic and clinical characteristics in inpatients in a large psychiatric institution in Beijing, China.A consecutive sample of 617 psychiatric inpatients formed the study sample. Basic sociodemographic and clinical data including serum prolactin level were collected.The prevalence of hyperprolactinemia was 55.9% in the whole sample, and 56.8% and 43.2% for women and men, respectively. The corresponding figures were 59.6%, 40.0%, 53.6%, and 50.8% in schizophrenia spectrum disorders, major depression, bipolar disorders, and other psychiatric disorders, respectively (p = 0.09). In univariate analyses, patients having hyperprolactinemia were younger, more likely to receive risperidone, amisulpride, and first-generation antipsychotics, but less likely to receive clozapine and aripiprazole. In multiple logistic regression analysis, hyperprolactinemia was independently associated with younger age, more use of risperidone or amisulpride and first-generation antipsychotics, and less use of clozapine and aripiprazole (r(2) = 0.197).Hyperprolactinemia is very common in Chinese psychiatric inpatients. Given the potentially harmful consequences of hyperprolactinemia and its preventable nature, effective measures to lower the frequency hyperprolactinemia in patients with major psychiatric disorders should be implemented in Chinese mental health facilities.
- Resistant prolactinoma: Is it monoclonal or polyclonal? [Journal Article]
- Indian J Endocrinol Metab 2013 Oct; 17(Suppl 1):S139-41.
Prolactinomas are solitary benign neoplasms and resistance to dopamine agonists occur in a small percentage of prolactinomas. Multiple pituitary adenomas are reported in less than 1% of pituitary adenomas and rarely result in resistant prolactinoma. We recently encountered an interesting patient of hyperprolactinemia with multiple pituitary microadenomas. Dopamine agonist use resulted in prolactin normalization and subsequent pregnancy resulted in drug withdrawal. Repeat evaluation after delivery showed a macroprolactinoma and dopamine agonist therapy resulted in biochemical cure without reduction in tumor size. We report the case for its presentation with multiple microadenomas progressing to macroprolactinoma suggesting polyclonal in origin.