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 < 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.

Evaluation of maternal serum prolactin in pregnant women with gestational Diabetes mellitus

Maintenance of normal glucose metabolism during pregnancy is of particular importance. Prolactin may be a mediator in pathogenesis of impaired glucose metabolism. This study aimed to assess the levels of maternal serum prolactin in pregnant women with gestational Diabetes mellitus (GDM). This prospective observational study was done at AL– Emamain AL- Kadhemain Medical City/ Department of Obstetrics and Gynecology in Baghdad/ Iraq during the period from 1st March to 1st October 2018 on 150 pregnant women who were referred for OGTT for different indications. For all included women, maternal serum prolactin level and 75 gm OGTT was performed. The results showed that the mean±SD of maternal serum prolactin levels for all included women was (135.14±22.67) ng/ml and there was significantly negative correlation with (1hr) and (2hr) blood glucose levels of 75 gm OGTT at p value (0.027), (0.003) respectively. Out of 150 women included in the study (52) women diagnosed to have GDM and (98) women to have normal glucose tolerance. The mean±SD of maternal serum prolactin level was (123.6±13.7) ng/ml in GDM group which is significantly lower in comparison with mean ±SD (141.3±24.1) ng/ml in normal group at p value (0.0001). It can be concluded that women with GDM showed significantly lower serum prolactin levels in comparison with levels in women with normal glucose tolerance.

Satb2 regulates the development of dopaminergic neurons in the arcuate nucleus by Dlx1

Dopaminergic (DA) neurons in the arcuate nucleus (ARC) of the hypothalamus play essential roles in the secretion of prolactin and the regulation of energy homeostasis. However, the gene regulatory network responsible for the development of the DA neurons remains poorly understood. Here we report that the transcription factor special AT-rich binding protein 2 (Satb2) is required for the development of ARC DA neurons. Satb2 is expressed in a large proportion of DA neurons without colocalization with proopiomelanocortin (POMC), orexigenic agouti-related peptide (AgRP), neuropeptide-Y (NPY), somatostatin (Sst), growth hormone-releasing hormone (GHRH), or galanin in the ARC. Nestin-Cre;Satb2flox/flox (Satb2 CKO) mice show a reduced number of ARC DA neurons with unchanged numbers of the other types of ARC neurons, and exhibit an increase of serum prolactin level and an elevated metabolic rate. The reduction of ARC DA neurons in the CKO mice is observed at an embryonic stage and Dlx1 is identified as a potential downstream gene of Satb2 in regulating the development of ARC DA neurons. Together, our study demonstrates that Satb2 plays a critical role in the gene regulatory network directing the development of DA neurons in ARC.

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.

Assessment of serum prolactin level in hepatic encephalopathy patient

Background: Hepatic encephalopathy (HE) is a complex neuropsychiatric disorder that arises in both acute and chronic liver disease. It is typified by the disturbance in consciousness and behavior, personality changes fluctuating neurological signs, asterisks or flapping tremors and distinctive EEG changes. This study was established to assess and evaluate the serum prolactin level in hepatic encephalopathy (HE) patient.Methods: The present cross-sectional study consisted a total 70 patients, out of those 35 were having HE and the rest 35 had no clinical evidence of HE. Those patients without clinical evidence of HE but having cirrhosis of liver, acute viral hepatitis and normal healthy controls.Results: Serum prolactin levels of patients of cirrhosis of liver with hepatic encephalopathy ranged from 37.6-210.7 ng/ml with a mean of 73.63±43.85 ng/ml. In patients, Prolactin levels were found significantly high in cirrhosis of liver patients with HE then cirrhosis of liver without HE patients (p<0.001). Level of serum prolactin in patients with hepatic encephalopathy with Fulminant hepatic failure (FHF) ranged from 30.6-119.7 ng/ml with a mean of 71.24±26.87 ng/ml. The values obtained from these are significantly higher as compared to those in normal healthy controls and those in acute viral hepatitis (p<0.001). Level of serum prolactin in patients of liver cirrhosis without hepatic encephalopathy ranged from 18.6-26.4 ng/ml with a mean of 21.48±2.43 ng/ml. These values are significantly higher than those found in normal healthy controls and those found in acute viral hepatitis (p<0.001). Mortality rate was 70% in patients of cirrhosis of liver with HE.Conclusions: Serum prolactin levels (SPL) are significantly higher in patients with complications such as hepatic encephalopathy and higher the levels, greater the severity. Hence, we conclude that level of serum prolactin can be used as a useful prognostic marker in patients with cirrhosis of the liver as well as an early indicator of its complications.

Acute Ischaemic Stroke With Hyperprolactinemia:A Case Report

Background: Macroincidentalomas were reported in 0.2% of patient underwent imaging (CT scans) for central nervous symptoms (1). In acute ischaemic stroke with hyperprolactinemia, the diagnosis of a double pathology of ischemic stroke and sellar tumour especially prolactinoma need to be considered. Hyperprolactinemia itself may be considered as a risk factor for ischemic stroke due to its thrombogenic effect (3). Clinical Case: A 47-year old man underlying hypertension and diabetes mellitus for 5 years presented with sudden onset of right sided body weakness associated with facial asymmetry and aphasia. No history of fever or trauma. Asymptomatic of hyperprolactinemia previously. On general examinations Glasgow Coma Scale 11/15 Eye 4 Verbal 1 Motor 6, blood pressure was unstable with readings of systolic 244mmHg and diastolic 142mmHg. Neurological examinations showed expressive aphasia, right hemianopia, right facial nerve palsy and absence of gag reflex. Cerebellar signs were negative. Motor function examinations of right upper and lower limbs showed hypertonia, reduce power of 2/5, normal reflexes and up going plantar response. Sensory functions of right upper and lower limbs were reduced. Clinically diagnosed as stroke with hypertensive emergency. CT brain showed multiple hypodensities due to recent infarct and incidental finding of an aggressive sellar mass. MRI brain showed left Middle Cerebral Artery territory infarct and an aggressive sphenoid sinus mass with suprasellar and bilateral cavernous sinus extension possibility of a macroadenoma. Serum prolactin level showed markedly hyperprolactinemia (21146 ng/ml, n 4.04 – 15.2 ng/ml) which level of 500ng/ml or greater is diagnostic of a macroprolactinoma (2). FSH level (0.929 IU/L, n 1.5-12.4 IU/L) and LH level (1.11 IU/L, n 1.7-8.6 IU/L) were low in this patient due to suppression of GnRH secretion from hypothalamus by prolactin. Testosterone level (0.15 nmol/L, n 8.64-29.0 nmol/L) was low secondary to low LH. Serum cortisol, growth hormone and TSH were normal. Platelet count and coagulation profiles were normal. The patient was treated conservatively in ward for acute ischaemic stroke and later was started on dopamine agonist cabergoline for hyperprolactinemia. Conclusion: This is a case report of acute ischaemic stroke with markedly hyperprolactinemia secondary to incidentaloma macroprolactinoma. Reference: (1)Freda PU, Beckers AM, Katznelson L, et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96 (4): 894-904.(2)Abha Majumdar and Nisha Sharma Mangal. Hyperprolactinemia. J Hum Reprod Sci. 2013 Jul-Sep; 6(3): 168–175.(3)Sankalp Kumar Tripathi, Pallavi Kamble, M.G. Muddeshwar. Serum Prolactin Level in Patients of Ischemic stroke. International Journal of Contemporary Medical Research 2016; 3(12): 3459-3460.

Forbes albright syndrome: galactorrhea–amenorrhea associated with a pituitary tumour: a case report

Forbes Albright syndrome is a hyperprolactinemia syndrome characterised by galactorrhea and amenorrhea associated with a pituitary tumour. Here we report a case of 30 years female who was admitted with menstrual irregularities for 4 months, galatorrhea and headache with recurrent episodes of loss of consciousness for 3months. Her serum prolactin level was highly raised. MRI brain (plain plus contrast) showed enlarged pituitary gland- pituitary macroadenoma. She was diagnosed as a case of Forbes Albright Syndrome and was treated with Tablet Cabergoline. With the medication, size of her tumour markedly reduced and symptoms resolved as she was followed up after 3 months.