Prolactin level correction in restoration of menstrual cycle in obese women

Obesity is a common problem among women of reproductive age. There are data from clinical and experimental studies indicating the role of hyperprolactinemia in the development of metabolic syndrome, as well as the metabolic benefits of treating hyperprolactinemia.Research objective: to evaluate the clinical efficacy of Vitex Agnus Castus standardized extract on hormonal and metabolic status in women with menstrual cycle disorders and obesity.Materials and methods. 60 women aged 19 to 35 years with obesity and menstrual cycle disorders with laboratory-confirmed insulin resistance and prolactin near the upper limit of the reference values or was slight increase were examined. All the patients were given recommendations for lifestyle modification. 30 of them, who formed the main group, received Cyclodynon. 30 patients of the control group were not prescribed Cyclodynon therapy.Results. At the end of the treatment, the menstrual cycle was normalized in 93.3% patients of the main group, and in 66.3% patients of the control group (p < 0.05). Ovulation signs were detected in 86.67% women of the main group and only in 30.0% women of the control group (p < 0.05). The mean prolactin value and the HOMA index were significantly lower in the main group; prolactin level did not exceed the physiological values in 86.67% women in the main group after 6 months, and in 40.0% of the control group, p < 0.05. There was a decrease in body mass index and waist/hip circumference ratio in patients of the studied groups; the dynamics was slightly higher in the main group but did not differ significantly. Conclusions. Cyclodynon is effective for the treatment of menstrual cycle disorders and metabolic disorders in women with obesity and metabolic syndrome. Good tolerability, absence of side effects, and sufficient efficacy of Cyclodynon allow it to be recommended as the drug of choice in patients with prolactin levels near the upper limit of the reference values or a slight increase of it and in patients with intolerance to synthetic dopamine agonists.

EPID-13. PREDICTIVE VALUE OF SERUM PROLACTIN LEVEL TO THE TUMOR SIZE RATIO FOR PREOPERATIVE DIAGNOSIS OF PROLACTIN-PRODUCING PITUITARY ADENOMA

PURPOSE Preoperative diagnosis of prolactinomas is critical because medication of dopamine agonists instead of surgical resection has been regarded as a primary treatment. However, serum prolactin level alone is suboptimal for differentiating the prolactin producing adenoma or hyperprolactinemia-causing NFPAs. The author investigated the use of ratio of PRL levels to the tumor size as the optimal cutoff value for prolactin-producing tumor, comparing with the NFPA. METHOD We performed a retrospective review of patients who underwent the transsphenoidal surgery (TSS) for pituitary lesions in the single institute between January 2015 to May 2020. A total of 223 patients with hyperprolactinemia at the initial diagnosis were analyzed in the study, including NFPA patients (n=175) and prolactinoma patients (n=48). Receiver operating curve (ROC) analyses were performed for serum prolactin levels (PRL) and serum prolactin levels/tumor maximal diameter (PRL/MD). RESULT Prolactinoma group showed higher median values in serum PRL (258.6 μg/L) and smaller maximal tumor diameter (16.6 mm), compared to those of NFPA group (serum PRL 44.4 μg/L, p-value = 0.002 and MD 23.9 mm, p-value &lt; 0.001). A moderate correlation was found between serum prolactin level and maximal diameters in prolactinomas (r=0.43, p=0.002), whereas a weak relationship was confirmed in NFPAs (r=0.17, p=0.028). The cutoff was 8.93 μg/L*mm (area under the curve [AUC] = 0.94) for PRL/MD and 99.43 μg/L for PRL (AUC = 0.91). In prolactinomas, there was no statistical difference between the PRL/MD of macroadenomas (n=36, 21.7μg/L*mm) and microadenoma (n=12, 16.8μg/L*mm) (p=0.109). CONCLUSION The serum PRL levels and tumor size exhibited stronger linear correlation in prolactinomas than in NFPAs. The PRL/MD ratio showed better diagnostic value for differentiating two pathologies than the serum PRL levels alone. These findings suggest PRL/MD ratio may be an alternative method to preoperative diagnosis of prolactinomas differentiating from hyperprolactinemia-causing NFPAs.

Association of Serum Prolactin Level with Preeclampsia

Introduction:Preeclampsia is a potentially fatal disorderof pregnant women; it remains an important cause of maternal mortality throughout the world. More than 50,000 maternal deaths occur worldwideeach year. Various researchers of different countries suggested an association of increase level of serumprolactin in preeclamptic patient. Estimation of serum prolactin level in pregnancy may be helpful in diagnosis of preeclampsia. Objective: Theobjective of the study is to observe the association of serum prolactin level with severity of preeclampsia. Materials and Methods: This cross-sectionalstudy was conducted from March 2020 to February 2021 in the Department of Laboratory Medicine, Department of Fetomaternal Medicine and Obstetrics and Gynecology, BSMMU and Dhaka Medical College Hospital, Dhaka. Fifty diagnosed patients of preeclampsia who fulfilled the inclusion and exclusioncriteria were selected as study population. At the same time 50 normal pregnant women were taken in another group. In both groups gestational age was calculated from last Menstrual date and confirmed by early ultrasound which wasdone at <14 weeks. Then serum prolactin level was calculated. Results: The mean serum prolactin level was 226.56±81.23 µg/L in mild and 394.53±78.75 µg/L in severe preeclampsia. The difference was statistically significant (p=0.001) between two groups.In ROC analysis cut off value of serum prolactin level was 118 μg/L.The area under curve (AUC) of serum prolactin was 0.923 (95% CI; 0.869-0.978). Spearman’s rank correlation coefficient test showed significant positive correlation (r=0.719,p=0.001) between serum prolactin level with severity of preeclampsia. This finding of the study revealed that serum prolactin level was increased with preeclampsia and was positive correlation with severity. Conclusion: Because of significantsensitivity and specificity, serum prolactin level maybe used as an important tool to diagnose preeclampsia and its severity.

Prevalence of Macroprolactinemia in Patients with Hyperprolactinemia Using Roche Elecsys Platform in a Large Tertiary Referral Center in UAE

<b><i>Objectives:</i></b> Macroprolactin (macroPRL) excess is an important cause of hyperprolactinemia. Several prolactin assays have high reactivity to macroPRL. However, macroPRL screening is not routinely performed in many labs. This study aimed to evaluate the prevalence of macroprolactinemia (MP) in patients with elevated prolactin using the Roche Elecsys assay in a large tertiary center in UAE. <b><i>Materials and Methods:</i></b> Consecutive samples of patients with elevated prolactin presenting to Tawam Hospital from June to August 2018 were evaluated for MP. Polyethylene glycol (PEG) was used to precipitate macroPRL. Monomeric prolactin recovery cutoff ≤50% was used to determine the prevalence of MP. <b><i>Results:</i></b> A total of 180 patients with elevated prolactin were included in the study with a mean age of 33.1 ± 11.9 years. The majority were women (87.2%), and about 77.8% were newly diagnosed patients with hyperprolactinemia. The main indications for prolactin testing were menstrual irregularity (<i>n</i> = 121), infertility (<i>n</i> = 11), galactorrhea (<i>n</i> = 11), and sellar masses (<i>n</i> = 12). MP was present in 8.3% of the patients. The median (IQR) of total prolactin level was 740.5 (579–1,085) IU/m before PEG precipitation and was not significantly different between MP and true hyperprolactinemia cases. Three patients with MP had pituitary MRI evaluation, which was normal. Eight patients with MP were treated with cabergoline. <b><i>Conclusion:</i></b> One in 12 patients with hyperprolactinemia had MP on the Roche Elecsys assay defined as the cutoff recovery of ≤50% post-PEG precipitation. Physicians should be aware of the prolactin assay used in their labs, and we recommend routine macroPRL assessment in mild hyperprolactinemia samples in labs using the Roche Elecsys platform.

Surgery and Medical Treatment in Microprolactinoma: A Systematic Review and Meta-Analysis

Objective. Dopamine agonists (DAs) are recommended as the first-line treatment for prolactinomas; however, tumour recurrence after drug withdrawal remains a clinical problem. Recent studies have reported high remission rates via surgery in microprolactinomas. The aim of this systematic review and meta-analysis was to compare the clinical result of DA treatment with surgery as initial therapy in patients with treatment-naive microprolactinoma. Methods. A comprehensive literature search for studies and reports regarding microprolactinoma patients treated with DAs and/or surgery published between January 1970 and November 2020 was conducted using four electronic databases (PubMed, Embase, Google Scholar, and the Cochrane Library). Clinical treatment outcome was evaluated by the biochemical remission of serum prolactin level to normal after treatment. The I2 statistic was used to quantify heterogeneity. Pooled data were analysed according to a random effect model. Results. Eighteen studies with 661 patients were included for analysis. The DA treatment group achieved a higher remission rate at ≥12 months follow-up (96% vs. 86%; P = 0.019 ). Surgery showed a higher remission rate than the DA treatment group after the treatment withdrawal (78% vs. 44%; P = 0.003 ). Patients with preoperative prolactin level of ≤200 ng/mL had a higher remission rate than patients with preoperative prolactin level of >200 ng/mL (92% vs. 40%; P = 0.029 ). Conclusion. Surgery showed a high remission rate in treatment-naive microprolactinoma patients after treatment withdrawal and may be an alternative first-line treatment strategy in addition to DAs, particularly in patients with a preoperative prolactin level of ≤200 ng/mL.

Polycystic ovarian syndrome and pituitary macroadenoma a deadly combination with good outcome

We are presenting here a case of polycystic ovarian syndrome, an endocrine disorder, afflicting 5-13% females of reproductive age, causing 70-80% infertility associated with pituitary macroadenoma i.e. size >10 mm & prolactin level >250 ng/mI. PCOS has a higher relationship with metabolic disturbance and hypothalamic-pituitary-ovarian axis function disorder. Prolactinoma is present in about 50% women with hyperprolactinemia and 33% present with galactorrhea. Our patient was a 22 yrs nulligravida married since 3 yrs first presenting 5 yrs back with complaints of secondary amenorrhea with galactorrhea and infertility. On evaluation she was diagnosed as PCOS and pituitary macroadenoma on MRI. We medically treated her with tab. cabergoline in consultation with endocrinologist and neurosurgeons opinion. Being a compliant patient with regular follow up she conceived twice with good outcome and breastfed her babies on medical management only. Now she has 2 children (male child of 3 yrs and 1 month). Dilemma in management options will be discussed.

Serum Prolactin Level to Tumor Size Ratio as a Potential Parameter for Preoperative Differentiation of Prolactinomas from Non-Functional Pituitary Adenomas

INTRODUCTIONPreoperative diagnosis of prolactinomas is critical because dopamine agonists have been regarded as a primary treatment modality. However, serum prolactin level alone is suboptimal for differentiating between prolactinomas and hyperprolactinemia-causing non-functioning pituitary adenomas (NFPAs). The authors investigated more effective parameter for differentiating prolactinomas and NFPAs by using the adenoma size. METHODS We performed a retrospective review of patients who underwent trans-sphenoidal surgery for pituitary lesions in a single institute between January 2015 and May 2021. Using the receiver operating curve (ROC) analyses, we compared performances of serum prolactin levels (PRL), a ratio of serum PRL levels to maximal tumor diameter (MD) (PRL/MD; PDR1), and MD squared (PRL/(MD)2; PDR2) in preoperative diagnosis of prolactinomas. RESULTS 223 patients with NFPAs (n=175) and prolactinomas (n=48) were included in the analysis. The prolactinoma group showed higher serum prolactin (258.6 ㎍/L) and smaller MD (16.6 mm) than those in the NFPA group (44.4 ㎍/L and 23.9 mm; both p-values < 0.001). Among diagnostic parameters, PDR2 exhibited the optimal diagnostic performance with the cutoff value of 0.83 [㎍/L]/mm2 (area under the curve [AUC] = 0.945), compared to the PDR1 (8.93 [㎍/L]/mm with AUC 0.938) and PRL (99.4 ㎍/L with AUC 0.910). PDR2 still maintained superior performance in the validation study than PDR1 and PRL (Accuracy of 94.8%, 91.8%, and 75.8%, respectively).CONCLUSIONS PDR2 provided the best performance of three parameters in preoperative discrimination of prolactinomas from NFPAs with hyperprolactinemia, and could contribute to select patients who benefit from medical treatment primarily.

Ovulation Induction in Patients with Polycystic Ovarian Syndrome (PCOS) & Hyperprolactinemia (HPRL): Efficacy of Letrozole (LE) Combined with Cabergoline (CE) in Comparison to (LE) Alone

Objectives: (PCOS) is the most common cause of anovulatory infertility, with majority of patients having mild (HPRL). (CE), a dopamine receptor agonist, inhibits prolactin secretion, leading to better ovulatory response. (LE), an aromatase inhibitor, without adverse effects on endometrium & induces fewer mature follicles with less risk of OHSS. Our aim was to investigate effects of combined (LE) & (CE) in comparison to (LE) alone on ovulation & clinical pregnancy rates in (PCOS) patients with (HPRL). Patients & Methods: 180 women with (PCOS) and of 22-38 years old, were enrolled in a hospital based clinical trial. Patients randomly allocated into 2 groups, (A&B). All with a serum prolactin > 32 ng/ml. Patients in (A): (92) were given (LE), 5mg for 5days: (3 – 7 of the cycle)/3 cycles and (CE), 0.5mg weekly for 12 weeks. Those in (B): (88) received only (LE), same dose & duration as in (A). All patients were matched for their age and BMI. Exclusion criteria: other causes of (HPRL). Outcome measure: ovulation rate & detection of both chemical & clinical pregnancies by βhCG and ultrasound of fetal cardiac activity, 2-4 weeks after missed period. Follow-up for 6 months. Data analysis by using SPSS version for windows, P-value significant if (< 0.05). Results: 3 patients from (A) & 5 from (B) had drug side effects and were excluded. None of patients were lost during the follow-up period. In (A), difference between mean serum prolactin level before & after treatment was statistically significant (P<0.001): 48.3±4.2ng/ml and 8.1±5.2ng/ml, respectively. No significant decrease of prolactin level in (B) (P >0.05). After treatment, BMI in (A) 24.1± 3.2, & 24.2 ± 3.6 in (B) (P=0.567). (56.2%) of women in (A) became regularly menstruating but only (30.1%) in (B) (P< 0.05). Ovulation rate was higher in (A) (50.6%) in comparison to (B) (26.5%), (P<0.05). Clinical pregnancy rate in (A) (41.6%) and (21.6%) in (B) (P<0.05). Neither twin pregnancy, nor OHSS were recorded in both groups. Conclusions: The combination of (LE) & (CE) is superior to (LE) alone in management of anovulatory patients with (PCOS) and should be used as the first-line treatment for them